Hybrid Macrocyclic Polymers: Self-Assembly Containing Cucurbit[m]uril-pillar[n]arene

Supramolecular self-assembly by hybrid macrocycles containing both cucurbit[m]uril (CB[m]) and pillar[n]arene was discussed and summarized in this review. Due to different solubility, diverse-sized cavities, and various driving forces in recognizing guests, the role of CB[m] and pillar[n]arene in such hybrid macrocyclic systems could switch between competitor in capturing specialized guests, and cooperator for building advanced hybridized macrocycles, by controlling their characteristics in host–guest inclusions. Furthermore, both CB[m] and pillar[n]arene were employed for fabricating advanced supramolecular self-assemblies such as mechanically interlocked molecules and supramolecular polymers. In those self-assemblies, CB[m] and pillar[n]arene played significant roles in, e.g., microreactor for catalyzing particular reactions to bridge different small pieces together, molecular “joint” to connect different monomers into larger assemblies, and “stabilizer” in accommodating the guest molecules to adopt a favorite structure geometry ready for assembling.

Actually, the fabrication of a proper hybrid macrocyclic system by diverse macrocycles was not easy [32,34,35]. There were several difficulties in the design strategy and experimental procedure [36]. For example, the modification and functionalization of various macrocycles were usually challenging [37], in addition to coupling them together. If not adopting the proper design and efficient synthesis methods, the building of hybridized macrocycles might become not only overdesigned, but also time-consuming [38,39]. In addition, during the construction, different behaviors of diverse macrocycles in molecul recognition should be controlled and balanced in order to achieve the purpose of functio and application [40,41]. For example, the different-sized host cavities [26] and vario driving forces [42,43] capturing guests should be paid attention during molecular reco nition. Furthermore, the role of diverse macrocycles in a hybrid system should be ful considered and taken advantage of. For example, some macrocycles could promote t solubility of the integrated system [44][45][46][47], while other macrocycles could contribute catalyzing particular reactions during the process of self-assembly [48][49][50].
Pillar [n]arene [51,52] (Chart 1) was discovered in 2008 and has been widely used the process of supramolecular self-assembly [53,54]. Due to its unique physiochemic properties and symmetric structures, pillar[n]arene usually has poor solubility in aqueo solutions [55]. Thus, such a macrocycle requires particular modification to possess t ability of solubilizing in aqueous solutions [56][57][58]. Several functional groups have be involved including carboxylate and ammonium salts [59][60][61][62]. However, the method an choice of dissolving pillar[n]arene in aqueous solutions were limited. It will be interestin to investigate whether other water-soluble macrocycles could integrate with p lar[n]arene in a hybrid system and promote its solubility in aqueous solution or not. O favorite candidate is cucurbit[m]uril (CB[m], Chart 1) [63,64], composing cyclic repeatin glycoluril. Furthermore, it will be fantastic to learn whether the addition of CB[m] w play other roles in the hybrid system, or not. It is already known that the hydrophob cavity of CB[m] can show similar molecular recognition as that of pillar[n]arene towar various guests, and CB[m] is commercially available with different-sized cavities, whi can enrich the host-guest interaction in the possible integrated hybrid macrocyclic syste [65,66].
In this review, we will discuss and summarize the recent progress in building se assembly containing both CB[m] and pillar[n]arene. Due to the possession of similar ca ities, both present in the integrated hybrid system could show competition in includin similar/same guests. Thus, a valuable synthesis/preparation strategy was employed in t hybridized system to balance and control their different molecular recognition. Except f competition, the relationship between them in an integrated system also shows cooper tion in accommodating diverse guests, in addition to providing the possibility of bridgin smaller pieces together for hierarchical self-assemblies such as mechanically interlock molecules [67][68][69][70][71] and supramolecular polymers [72][73][74][75]. Interestingly, due to the part ular structure and physiochemical properties, CB[m] could play diverse roles in t CB[m]-pillar[n]arene hybrid macrocyclic system such as acting as "microreactor" and m lecular "joint" [76][77][78]. Finally, because the self-assembly containing CB[m]-pillar[n]are hybrid macrocyclic system is still under development, we will try to raise some scienti and technical issues in this review, and propose considerable challenges for future r search.

The Competition and Cooperation between CB[m] and Pillar[n]arene as the Host
As significant hosts, both CB[m] and pillar[n]arene could show different characteristics in host-guest complexation, due to diverse-sized cavities and various driving forces in recognizing guests. Interestingly, both could exhibit very strong capacity in molecular recognition towards the same guest. Thus, if placed under specialized conditions, they could definitely show competition in efficiently capturing those particular guests. Further effort has been made in controlling and balancing their diverse performances in molecular recognition by building integrated self-assemblies, i.e., hybrid macrocyclic systems.
Due to the lock-and-key principle in supramolecular chemistry [79,80], CB[m] and pillar[n]arene usually exhibit different behaviors in recognizing guest molecules with diverse associate constants, (Ka). Thus, CB[m] could be used as an extra tool to control the physiochemical properties of self-assembled pillar[n]arene and its host-guest complexes. For example, Ref. [79], in comparison with the monomer M1 (Scheme 1) and short ethylene oxide chains-bearing pillar [5]arene (P1, Scheme 1), pillar [5]arene perfunctionalized with ten outer triethylene oxide groups (P2, Scheme 1) could not only have improved solubility in water, but also exhibited the lower critical solution temperature (LCST) behavior [81], i.e., sharp transition and narrow hysteresis (2 • C), due to the possession of both longer oligomeric ethylene oxides and macrocyclic skeletons [79]. Additionally, instead of shorter viologen salts such as G1 (Scheme 1), P2 could include the didecylviologen salt (G2, Scheme 1) in the stoichiometry of 1/1 with the Ka as (4.3 ± 0.5) × 10 3 M −1 at 25 • C, due to stronger hydrophobic and charge transfer interactions. Interestingly, the clouding point (T cloud ) of P2 could be controlled by the concentration and amount of G2, changing from 25 to 60 • C. Particularly, due to that cucurbit [7]uril (CB [7], Scheme 1) could include viologen salts also in 1/1 molar ratio but with the stronger Ka as high as 105 × M−1, CB [7] was used a competitive host to exclude G2 from P2 (Table 1), leading to the decrease of T cloud in the system containing G2 and P2 to 47 • C [79]. Furthermore, the host-guest inclusion controlled reversible turbid-to-clear/clear-to-turbid transition could be achieved by the subsequent addition of G2 and CB [7] in the solution of P2 ( Figure 1). Actually, both CB[m] and pillar[n]arene could fully utilize their capacities of capturing guests to further affect the morphologies of guests-based self-assemblies [82].

The Competition and Cooperation between CB[m] and Pillar[n]arene as the Host
As significant hosts, both CB[m] and pillar[n]arene could show different characteristics in host-guest complexation, due to diverse-sized cavities and various driving forces in recognizing guests. Interestingly, both could exhibit very strong capacity in molecular recognition towards the same guest. Thus, if placed under specialized conditions, they could definitely show competition in efficiently capturing those particular guests. Further effort has been made in controlling and balancing their diverse performances in molecular recognition by building integrated self-assemblies, i.e., hybrid macrocyclic systems.
Due to the lock-and-key principle in supramolecular chemistry [79,80], CB[m] and pillar[n]arene usually exhibit different behaviors in recognizing guest molecules with diverse associate constants, (Ka). Thus, CB[m] could be used as an extra tool to control the physiochemical properties of self-assembled pillar[n]arene and its host-guest complexes. For example, ref [79], in comparison with the monomer M1 (Scheme 1) and short ethylene oxide chains-bearing pillar [5]arene (P1, Scheme 1), pillar [5]arene perfunctionalized with ten outer triethylene oxide groups (P2, Scheme 1) could not only have improved solubility in water, but also exhibited the lower critical solution temperature (LCST) behavior [81], i.e., sharp transition and narrow hysteresis (2 °C), due to the possession of both longer oligomeric ethylene oxides and macrocyclic skeletons [79]. Additionally, instead of shorter viologen salts such as G1 (Scheme 1), P2 could include the didecylviologen salt (G2, Scheme 1) in the stoichiometry of 1/1 with the Ka as (4.3 ± 0.5) × 10 3 M −1 at 25 °C, due to stronger hydrophobic and charge transfer interactions. Interestingly, the clouding point (Tcloud) of P2 could be controlled by the concentration and amount of G2, changing from 25 to 60 °C. Particularly, due to that cucurbit [7]uril (CB [7], Scheme 1) could include viologen salts also in 1/1 molar ratio but with the stronger Ka as high as 105 × M−1, CB [7] was used a competitive host to exclude G2 from P2 (Table 1), leading to the decrease of Tcloud in the system containing G2 and P2 to 47 °C [79]. Furthermore, the host-guest inclusion controlled reversible turbid-to-clear/clear-to-turbid transition could be achieved by the subsequent addition of G2 and CB [7] in the solution of P2 ( Figure 1). Actually, both CB[m] and pillar[n]arene could fully utilize their capacities of capturing guests to further affect the morphologies of guests-based self-assemblies [82]. Scheme 1. Chemical structures of pillar [5]arene P1 and P2, CB [7], guest molecules G1 and G2, and monomer M1.  Because of the different-sized cavities, CB[m] and pillar[n]arene could also adjust their own cavities with proper sizes, i.e., choose the pair of hosts with proper sized cavities, to present the similar Ka towards the specialized guest. However, they might have different types of host-guest inclusions in accordance with diverse driving forces. For example, with the similar Ka of around 10 4 × M −1 , CB[7] (Scheme 1) could form inclusion with the guest of hemicyanine dyes (G3, Scheme 2) in the stoichiometry of 1/1 due to the ion-polar interaction, while pillar [6]arene P3 (Scheme 2) could interact with G3 in 2/1 molar ratio with a sandwiched binding model due to the intermolecular interaction with the electron donor-acceptor, i.e., exo-wall complexation, where the guest was not included into the cavity of P3 [83]. Thus, by taking advantage of their own characteristics such as various Ka and binding model in recognizing guests, CB[m] and pillar[n]arene could cooperate together to interact with guest molecules in an integrated hybrid macrocyclic system. For example, ref [84], due to the ion-dipole and CH … O interactions as indicated by computational studies [85] using a semi-empirical tight binding method, the ring-on-ring hybrid macrocyclic host systems were just prepared by integrating CB [10] and polycationic perfunctionalized pillar [5]arene P4 (Scheme 3) together, where the complex ratio could be tuned from 1/2 to 1/1 (Figure 2), as confirmed by 1 H NMR titration. Interestingly, the weaker interaction between P4 and CB[8] (Scheme 3) further revealed that the size match between pillar[n]arene and CB[m] was also vital for successfully building a hybrid macrocyclic composite. Particularly, characteristics in recognizing various guests by both cavities of CB [10] and pillar [5]arene could be further controlled and balanced, leading to either the formation of complicated multiple complexes or the damage of the hybrid macrocyclic host systems (Table 1)  Thus, by taking advantage of their own characteristics such as variou ing model in recognizing guests, CB[m] and pillar[n]arene could coopera interact with guest molecules in an integrated hybrid macrocyclic system ref [84], due to the ion-dipole and CH … O interactions as indicated by compu ies [85] using a semi-empirical tight binding method, the ring-on-ring hybr host systems were just prepared by integrating CB [10] and polycationic per pillar [5]arene P4 (Scheme 3) together, where the complex ratio could be tun 1/1 (Figure 2), as confirmed by 1 H NMR titration. Interestingly, the weak between P4 and CB[8] (Scheme 3) further revealed that the size match lar[n]arene and CB[m] was also vital for successfully building a hybrid ma posite. Particularly, characteristics in recognizing various guests by both cav and pillar [5]arene could be further controlled and balanced, leading to mation of complicated multiple complexes or the damage of the hybrid ma Thus, by taking advantage of their own characteristics such as various Ka and binding model in recognizing guests, CB[m] and pillar[n]arene could cooperate together to interact with guest molecules in an integrated hybrid macrocyclic system. For example, ref [84], due to the ion-dipole and CH . . . O interactions as indicated by computational studies [85] using a semi-empirical tight binding method, the ring-on-ring hybrid macrocyclic host systems were just prepared by integrating CB [10] and polycationic perfunctionalized pillar [5]arene P4 (Scheme 3) together, where the complex ratio could be tuned from 1/2 to 1/1 (Figure 2 was also vital for successfully building a hybrid macrocyclic composite. Particularly, characteristics in recognizing various guests by both cavities of CB [10] and pillar [5]arene could be further controlled and balanced, leading to either the formation of complicated multiple complexes or the damage of the hybrid macrocyclic host systems (Table 1). Due to the possession of two independent hybrid cavities (Figure 2), both 1-pentanesulfonate (G4, Scheme 3) and 9,9 -spirobifluorene (G6, Scheme 3) could be included by the hybrid macrocycles via the cavities of pillar [5]arene and CB [10], exhibiting strong Ka as (3.8 ± 0.4) × 10 6 and (3.3 ± 0.7) × 10 5 M −1 , respectively. However, the butane-1,4-disulfonate (G5, Scheme 3) could trigger the disassembly of hybrid macrocycles P4•CB [10], and precipitate CB [10] in the solution phase ( Figure 2).

The Preparation of Mechanically Interlocked Molecules Containing CB[m] and Pillar[n]arene
Except for utilizing their diverse characteristics for promoting competition and cooperation in molecular recognitions, both CB[m] and pillar[n]arene were further employed for fabricating advanced mechanically interlocked molecules (MIM) by fully considering the CB[m]-catalyzed alkyne-azide 1,3-dipolar cycloaddition, namely, "click" reaction [86,87], in addition to the strong capacity of pillar[n]arene in accommodating and stabilizing specialized linear cationic substrates [88]. In other words, the molecular "rod" in building MIM could be captured by enough pillar[n]arene moieties with an expected rigid and linear geometry, while CB[m] could hold the molecular "stoppers" and promote the formation of the "bridge" between the "rod" and "stoppers" by "click" reactions. Finally, both CB[m] and pillar[n]arene acted as the "wheel" in the obtained MIM.

The Preparation of Mechanically Interlocked Molecules Containing CB[m] and Pillar[n]arene
Except for utilizing their diverse characteristics for promoting competition and cooperation in molecular recognitions, both CB[m] and pillar[n]arene were further employed for fabricating advanced mechanically interlocked molecules (MIM) by fully considering the CB[m]-catalyzed alkyne-azide 1,3-dipolar cycloaddition, namely, "click" reaction [86,87], in addition to the strong capacity of pillar[n]arene in accommodating and stabilizing specialized linear cationic substrates [88]. In other words, the molecular "rod" in building MIM could be captured by enough pillar[n]arene moieties with an expected rigid and linear geometry, while CB[m] could hold the molecular "stoppers" and promote the formation of the "bridge" between the "rod" and "stoppers" by "click" reactions. Finally, both CB[m] and pillar[n]arene acted as the "wheel" in the obtained MIM.

The Preparation of Supramolecular Polymer containing CB[m] and pillar[n]arene
As shown in the above examples, the CB[m]-catalyzed "click" reactions were able t produce the "angular" chemical structures, acting as the "stopper" in fabricating th space-limited self-assemblies such as MIM. If preparing infinite polymeric structure both CB[m] and pillar[n]arene mainly performed as the molecular "joint" to accommodat linear guests and direct the structural geometry of larger supramolecular assemblies.

The Preparation of Supramolecular Polymer containing CB[m] and pillar[n]arene
As shown in the above examples, the CB[m]-catalyzed "click" reactions were able to produce the "angular" chemical structures, acting as the "stopper" in fabricating the space-limited self-assemblies such as MIM. If preparing infinite polymeric structures, both CB[m] and pillar[n]arene mainly performed as the molecular "joint" to accommodate linear guests and direct the structural geometry of larger supramolecular assemblies.

The Preparation of Supramolecular Polymer containing CB[m] and pillar[n]arene
As shown in the above examples, the CB[m]-catalyzed "click" reactions were able to produce the "angular" chemical structures, acting as the "stopper" in fabricating the space-limited self-assemblies such as MIM. If preparing infinite polymeric structures, both CB[m] and pillar[n]arene mainly performed as the molecular "joint" to accommodate linear guests and direct the structural geometry of larger supramolecular assemblies.
Polymers 2022, 14, x 8 of P7 could further complex with imidazolium subunits on a specialized guest with nap thalene moieties on both ends (G13, Scheme 6), leaving the naphthalene subunits to b captured by CB [8]. Due to the enhancement of π-π stacking interactions of two nearb naphthalene groups by CB [8], supramolecular polymers P7⸧G13⊂CB[8] (Figure 4 an Table 2) could be prepared by those ternary components [93].

Overview and Outlook
In conclusion, supramolecular self-assembly based on hybrid macrocyclic system containing pillar[n]arene and CB[m] were summarized in this review. Both CB[m] an pillar[n]arene are significant hosts in the formation of host-guest complexation. Their b haviors in molecular recognition could be greatly affected by several issues such as sol bility in various solutions, various cavities and different driving forces in complexin guests. Both could exhibit strong competition in complexing the same/similar favori guest molecules. Except for competition, the capacity of CB[m] and pillar[n]arene in hos guest inclusion could be integrated into the hybrid macrocyclic system in order to enhan their performance in recognizing specialized guests. Furthermore, the structural skeleton of CB[m] and pillar[n]arene were employed for fabricating advanced supramolecular sel assemblies such as MIM and supramolecular polymers. In those self-assembled system hybrid hosts served as: 1) the molecular "joint" to connect different small molecular mo eties together into larger assemblies; 2) the "microreactor" to catalyze specialized rea tions which could further covalently couple building blocks into rigid architectures; an 3) the "stabilizer" to accommodate and stabilize guest molecules to adopt favorite mole ular geometry for advanced and complicated self-assembly.
Although much important work has been conducted in this area, several issu should be paid attention in future studies, for example: 1) More hybrid macrocyclic systems should be prepared in order to accomplish ad vanced chemical structures in addition to applicable functions, such as with new desig strategy and new components. To date, pillar[n]arene derivatives have rarely been use Scheme 6. Chemical structures of pillar [6]arene P7, and guests including G13-G15. P7 could further complex with imidazolium subunits on a specialized guest with naphthalene moieties on both ends (G13, Scheme 6), leaving the naphthalene subunits to be captured by CB [8]. Due to the enhancement of π-π stacking interactions of two nearby naphthalene groups by CB [8], supramolecular polymers P7⸧G13⊂CB[8] (Figure 4 and Table 2) could be prepared by those ternary components [93].

Overview and Outlook
In conclusion, supramolecular self-assembly based on hybrid macrocyclic systems containing pillar[n]arene and CB[m] were summarized in this review. Both CB[m] and pillar[n]arene are significant hosts in the formation of host-guest complexation. Their behaviors in molecular recognition could be greatly affected by several issues such as solubility in various solutions, various cavities and different driving forces in complexing guests. Both could exhibit strong competition in complexing the same/similar favorite guest molecules. Except for competition, the capacity of CB[m] and pillar[n]arene in hostguest inclusion could be integrated into the hybrid macrocyclic system in order to enhance their performance in recognizing specialized guests. Furthermore, the structural skeletons of CB[m] and pillar[n]arene were employed for fabricating advanced supramolecular selfassemblies such as MIM and supramolecular polymers. In those self-assembled systems, hybrid hosts served as: 1) the molecular "joint" to connect different small molecular moieties together into larger assemblies; 2) the "microreactor" to catalyze specialized reactions which could further covalently couple building blocks into rigid architectures; and, 3) the "stabilizer" to accommodate and stabilize guest molecules to adopt favorite molecular geometry for advanced and complicated self-assembly.
Although much important work has been conducted in this area, several issues should be paid attention in future studies, for example: 1) More hybrid macrocyclic systems should be prepared in order to accomplish advanced chemical structures in addition to applicable functions, such as with new design strategy and new components. To date, pillar[n]arene derivatives have rarely been used

Overview and Outlook
In conclusion, supramolecular self-assembly based on hybrid macrocyclic systems containing pillar[n]arene and CB[m] were summarized in this review. Both CB[m] and pillar[n]arene are significant hosts in the formation of host-guest complexation. Their behaviors in molecular recognition could be greatly affected by several issues such as solubility in various solutions, various cavities and different driving forces in complexing guests. Both could exhibit strong competition in complexing the same/similar favorite guest molecules. Except for competition, the capacity of CB[m] and pillar[n]arene in hostguest inclusion could be integrated into the hybrid macrocyclic system in order to enhance their performance in recognizing specialized guests. Furthermore, the structural skeletons of CB[m] and pillar[n]arene were employed for fabricating advanced supramolecular selfassemblies such as MIM and supramolecular polymers. In those self-assembled systems, hybrid hosts served as: 1) the molecular "joint" to connect different small molecular moieties together into larger assemblies; 2) the "microreactor" to catalyze specialized reactions which could further covalently couple building blocks into rigid architectures; and, 3) the "stabilizer" to accommodate and stabilize guest molecules to adopt favorite molecular geometry for advanced and complicated self-assembly.
Although much important work has been conducted in this area, several issues should be paid attention in future studies, for example: (1) More hybrid macrocyclic systems should be prepared in order to accomplish advanced chemical structures in addition to applicable functions, such as with new design strategy and new components. To date, pillar[n]arene derivatives have rarely been used as a type of effective supplement [94] for controlling CB[m]-based supramolecular systems by taking advantage of the particular external stimuli responsiveness of pillar[n]arene. In addition, several types of CB [m] have been used in preparation procedures, but only pillar[5/6]arene has been employed in the construction of a CB[m]-pillar[n]arene hybrid macrocyclic system. Actually, the performance of pillar[n]arene with larger cavities has more interesting behavior in host-guest complexes [95][96][97]. If they could be involved in the fabrication, the hybrid system will definitely possess different functions and "selling" points.
(2) Advanced and more complicated self-assemblies such as micelles and vesicles could be further prepared by taking advantage of different models such as self-assembled amphiphiles [98], which could be of interest in exploring the functions of cargo-delivering [99][100][101]. Furthermore, except for rotaxane, catenane [102][103][104][105] could also be prepared by integrating both pillar[n]arene and CB[m], enriching the family of MIM with mechanical bonds.
(3) Applications of CB[m] and pillar[n]arene-containing hybrid macrocyclic systems should be explored further. Currently, after forming inclusions in building self-assemblies such as MIM and supramolecular polymers, the cavities of pillar[n]arene and CB[m] will be fully occupied and have no further function. If those cavities in self-assembled systems could be freed, they might, accordingly, accomplish more interesting applications, such as for biomedicines, in addition to adsorption and separation in specialized industry [106][107][108].