Molecular self-assembly is prevalent, such as the formation of the double helix structure in deoxyribonucleic acid (DNA) strands, the folding of tertiary structures in ribonucleic acid (RNA) strands, the formation of functional proteins from amino acids, and the construction of micelles from lipid molecules in the aqueous phase. Inspired by the intricate self-assembly processes observed in nature, self-assembly strategies have played a crucial role in chemistry, physics, biology, and materials engineering. It has emerged as a vital "bottom-up" approach for synthesizing new materials. Diverse assembly strategies enable the creation of a wide range of structures suitable for various applications. The DNA structure can be regarded as the cross-linking product that connects DNA components with increasing levels of complexity [1][2][3][4]. The construction of hydrogen-bonded organic frameworks (HOFs) shares similarities with protein structure assembly (Fig. 1(a)), where one-dimensional (1D) isomolecular chains are commonly built through hydrogen bonding interactions between building blocks. These molecular chains are assembled using π-π interactions to create porous framework materials. Moreover, the forces inside and outside the molecular chains can be adjusted. For instance, we synthesized the first porous polymer-based HOF (PHOF-1) by creating a one-dimensional molecular chain through covalent bonding and assembling the chain using hydrogen bonding (Fig. 1(b)) [5]. Various HOFs can be constructed using strategies to meet specific application requirements.
Unlike how units are connected in metal-organic frameworks (MOFs) and covalent-organic frameworks (COFs), HOFs are composed of organic units, including pure organic molecules and metal-containing organic molecules, which are synergistically regulated by H-bonding interactions and other interaction forces (e.g., π-π interactions, etc.) [6][7][8][9][10][11][12][13][14][15]. The development of HOFs progressed at a slower pace than that of MOFs in the subsequent decades due to the challenge of their poor stability [16][17][18][19][20][21][22][23]. In 2010, Chen et al. reported a microporous HOF with permanent porosity, denoted as HOF-1 [24], which marked a significant milestone in establishing the concept of permanent porosity in HOFs. Subsequently, this achievement sparked a renewed interest in HOFs, propelling extensive investigations into their diverse applications. HOFs offer greater accessibility in preparation compared to MOFs. The framework of HOFs relies on Hbonding forces, enabling the H nodes within the framework to recover through interactions with H + in water or various solvents, including hydrochloric acid (e.g., the hydrogen bond reassociation mechanism for acid-assisted crystallization redemption (AACR)) (Fig. 2(a)) [25]. This characteristic of HOFs facilitates their recycling. Importantly, due to the absence of heavy metals in its synthesis, HOFs present a more promising outlook for biological applications than MOFs and other porous materials. HOFs also require mild synthesis conditions and have excellent solution processability (Fig. 2(b)). Currently, HOFs have shown great promise in various fields, including gas storage/separation [26][27][28][29][30][31][32][33][34][35], photocatalysis, chemical sensing, proton conduction, and biological applications. However, the stability of HOFs is still a concern due to the limitation of H-bonding. Despite the discovery of numerous HOFs, most fail to maintain structural integrity upon removing the guest molecules, leading to collapse. Therefore, enhancing the stability of HOFs is an urgent need.
This review focuses on recent advancements in HOFs, specifically in their photo-response, electro-response, and photovoltaic synergistic response. It also discusses existing strategies to enhance the stability of hydrogen-bonded organic frameworks.
HOFs are constructed similarly to MOFs and COFs, but with the distinction that HOFs utilize hydrogen bonds as the driving force for donor-receptor linkage. Typically, the structural units comprising the HOFs possess rigid characteristics that limit the free rotation and vibration of the construction pattern. The bonded by hydrogen bonds is attached to the rigid skeleton through a well-designed synthetic route. Subsequently, these binding sites self-assemble with adjacent components, completing the construction of HOFs through hydrogen bond interactions. Researchers are interested in the porosity of porous materials, which can be enhanced by controlling the bond length and employing bonding interactions based on orbital hybridization, such as sp 2 hybridization and sp 3 hybridization. The structural stability of HOFs can be improved by incorporating electrostatic forces, π-π interactions, and introducing multiple hydrogen bonds within the frameworks. However, increasing the number of bonds can also diminish the porosity; thus, balancing the stability and porosity of HOFs requires careful design and optimization. To address the balance between stability and permanent porosity in HOFs, researchers have explored various approaches to constructing porous HOFs using different motifs.
Initially, the diaminotriazines (DAT) moiety emerged as a wellknown synthon for researchers due to its possession of multiple hydrogen bonding sites (Fig. 3). Two-dimensional (2D) or threedimensional (3D) frameworks can be formed by attaching DAT molecules through hydrogen bonds. Furthermore, the interaction between two DATs can give rise to three distinct structural units, thereby increasing the diversity in DAT construction (Fig. 3(a)). Researchers have utilized these building blocks to fabricate a range of porous HOFs, including HOF-3 [36], HOF-4 [37], HOF-5 [38], HOF-6 [39], HOF-7 [40], HOF-9 [41], HOF-10 [42], and UPC-HOF-6 [43], etc. These HOFs have been studied for various applications and contributed significantly to the development of the field.
To this date, various strategies have been employed to improve the stability of HOFs. We classified the methods reported in recent literature into primarily five strategies: (1) π-π stacking, (2) highly interpenetrated networks, (3) chemically cross-linked HOFs, (4) charge-assisted H-bonds, and (5) mechanical synthesis.
π-π stacking. The π-π stacking interaction is a force that arises between two or more aromatic rings. Introducing π-π stacking in HOFs enhances the stability of two-dimensional HOFs that contain conjugated systems. Through the appropriate design of the organic frameworks, these HOFs can also form threedimensional frameworks with remarkable thermal stability and enhanced resistance to organic solvents as well as acidic and basic aqueous solutions, owing to the inert nature of the aromatic species. Miljanic and co-workers [44] have conducted an extensive investigation into the relationship between structure and porosity in porous molecular crystals. They synthesized over a dozen potential precursors for all-organic porous molecular crystals through a combination of Cu and Pd catalysis, inert atmosphere, and chemical and solvothermal synthesis. This series included variations in geometries, lengths, and the propensity for Hbonding and π-π stacking. Analysis of the crystal structures of the examined precursors revealed that both hydrogen bonding and π-π stacking capabilities are essential for the formation of porous structures.
Through careful observation of the crystal structures of SOF-7 [45] and HOF-TCBP [27] in 2018, it was discovered that the entire structure exhibited widespread and stable π-π interactions even after heating or water treatment. It demonstrated that selecting planar organic building blocks with substantial πconjugated systems facilitates the formation of structures featuring extensive and robust π-π interactions, ultimately leading to stable frameworks. Considering HOFs can be designed at the molecular level, this strategy can be implemented through the choice of appropriate organic building blocks with extended π-conjugated systems. For example, H 4 TBAPy, a planar molecule possessing a substantial π-conjugation system and four carboxylic acids, was selected as the building block for HOF construction. As expected, the resulting HOF, named PFC-1 (PFC = porous material from FJRSM, CAS), exhibited a high surface area of 2122 m 2 •g -1 and excellent chemical stability, which can withstand concentrated hydrochloric acid (12 M) for at least 117 days (Fig. 4) [25]. Strikingly, the thermal damage of PFC-1 can be easily remedied by AACR, which we have observed for the first time in HOFs.
Next, we sought to improve the stability of the frameworks using similar organic building blocks containing porphyrins. We hypothesized that altering the metal center of the porphyrin would result in a significant modification of the electronic structure of the macrocycles, the axial bonding/interactions, and the geometry of the peripheral substitutions. These changes can exert a substantial influence on the stability of HOFs [46]. To test this hypothesis, we incorporated various transition metal centers into porphyrins and synthesized HOFs possessing the same network topology. We found that the variation in metal centers in porphyrin led to significant changes in non-covalent interactions, orbital overlap, and molecular geometry, thus producing a series of metalloporphyrin HOFs with high surface area and excellent stability. For instance, the structure of one such HOF, PFC-73-Ni, was still intact after immersion in boiling water, concentrated hydrochloric acid, and heating to 270 °C.
Highly interpenetrated networks. The Interpenetrated network is a widely used approach to improve the stability of porous materials. The stability of HOFs can be effectively controlled by manipulating reactant concentrations, utilizing templates, and epitaxial synthesis. Interpenetration is a crucial structural characteristic of HOFs that fulfills multiple functions:
(1) enhancing the physical stability of the framework, (2) imparting flexibility and dynamic properties to the HOF structure, and (3) finely adjusting the pore environment. Additionally, it aids in comprehending the relationships between the structure and property of HOFs, providing valuable insights for the rational design of supramolecules tailored to specific applications [34,37,42,43,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62].
In 2018, Schroder et al. described an example of "interpenetration isomerism" in three-dimensional HOFs [53]. By exploiting the crystallization conditions for a peripherally extended triptycene, (abbreviated as H 6 PET, chemical formula: guest-accessible volume of about 80%. In PETHOF-2, five individual nets are related by translational symmetry and are stacked in an alternating fashion. The activated materials (PETHOF-1a) showed permanent porosity with Brunauer-Emmett-Teller (BET) surface areas exceeding 1100 m 2 •g -1 . It was found that the doubly interpenetrated PETHOF-1 was more stable than PETHOF-2 with a higher degree of interpenetration. Application of vacuum, even at 208 °C, resulted in complete loss of crystallinity in PETHOF-2, indicating superstructural instability, which can most likely be attributed to the highly strained hydrogen-bonded lattice. Synthetic control over the framework interpenetration could serve as a new strategy for constructing complex supramolecular architectures from simple organic building blocks.
By understanding the structure and properties of HOFs, we have utilized their multilevel structure to construct HOFs with intercalation. The structure of HOFs is dominated by molecular building blocks, which consist mainly of two indispensable parts: the backbone and hydrogen-bonding interactions. Changing either one of them could lead to a significant difference in the structure of the resulting materials [42,59]. This motivated us to study ligands with identical hydrogen-bonding interactions but different backbone geometries. 4,4',4''-benzene1,3,5-triyltris (benzoic acid) (H 3 BTB, also called 1,3,5-tris(4-carboxyphenyl) benzene and abbreviated as TCPB) and 4,4,'4''-(1,3,5-triazine-2,4,6triyl)tribenzoic acid (H 3 TATB), shown in Fig. 5(b), demonstrated such an example. H 3 TATB is a planar molecule with a conjugate, and H 3 BTB is a non-planar molecule. While PFC-12, a HOF constructed from H 3 TATB, has structural undulations, HOF-BTB, constructed from H 3 BTB, has no structural undulations (Fig. 5(b)) [63]. We hypothesized that the structural differences caused by these two similar ligands could be attributed to the slight twisting of the ligand H 3 BTB, which led to a large structure change due to surface energy. The surface energy change gave PFC-11 and PFC-12 a distinctive stepwise adsorption behavior under a specific pressure that arose from the motion between the intertwined hexagonal networks. In addition, the structural variation led to interpenetration only in the HOF with H 3 TATB, resulting in a difference in their stability-PFC-11 exhibited better stability than PFC-12 and PFC-13 [54].
Chemically cross-linked HOFs. Apart from the conventional strategies employed for constructing stable HOFs, researchers are actively exploring novel approaches, many of which have shown promising advancements. Ke et al. [64] devised hydrogen-bonded cross-linked organic frameworks (H C OFs) by leveraging the advantages of COFs and HOFs (Fig. 6(a)). These frameworks offer significant chemical stability, enabling selective adsorption of environmentally impactful guests while introducing novel elastic properties to the prevailing crystalline porous organic materials. This approach initially involved the crystallization of molecular precursors through multivalent hydrogen bonding interactions, yielding potentially porous molecular materials akin to HOFs. Notably, the solvent molecules within the crystals can remain intact prior to the subsequent chemical cross-linking step, ensuring the covalent cross-linking of these well-organized molecules without compromising their crystallinity. This approach proved to enhance the chemical stability of the network.
Charge-assisted H-bonds. Incorporating charge-assisted hydrogen-bonding interactions is another strategy employed to enhance the stability of HOFs. The charge interaction between ions can facilitate the construction of stable HOFs utilizing two ionic building blocks with opposing charges. In 2016, Ghosh et al. [65] reported two porous HOFs constructed using alkyne sulfonates and guanidinium ions (Fig. 6(b)). Thermogravimetric analysis (TGA) of HOF-GS-10 and HOF-GS-11 revealed an initial weight loss caused by the liberation of the adsorbed solvent guest molecules. These HOFs demonstrated exceptionally high proton conductivity (0.75 × 10 -2 and 1.8 × 10 -2 S•cm -1 , respectively) under humidified conditions, attributed to their ionic skeleton and additional proton source (from the ionic backbones built through arene sulfonates and guanidinium ions) [67]. In addition, these compounds exhibited low activation energy and higher proton conductivity than other porous crystalline materials, such as MOFs and COFs, even under ambient conditions of low humidity and moderate temperature (30-320 °C). Furthermore, when HOF-GS-10 and HOF-GS-11 developed cracks on their crystal surfaces caused by elevated temperatures or other factors, their crystallinity can be restored by immersing the HOFs in their mother liquor (acetone/MeOH, p-xylene/MeOH). This work suggests that combining ionic building units in frameworks is a viable method for creating stable HOFs. Mechanical synthesis. The conventional synthesis methods for HOFs, such as hydrothermal synthesis and environmental diffusion, often suffer from time-consuming procedures, limited reproducibility, and the introduction of impurities that disrupt the self-assembly process. These challenges are primarily attributed to the low bond energy and activation energy of H-bonds, making these bonds susceptible to structural heterogeneity (varied linkages, mismatched stacking) and H-bond formation with solvents. Recently, our research group developed a novel synthesis method to overcome these problems. According to collision theory, successful collision reactions between molecules require adequate energy in the correct direction. Due to their limited energy, molecules often cannot induce effective collisions to form covalent and coordination bonds, as these bonds possess relatively high activation energies. On the other hand, H-bonds are more likely to form through mechanical collisions due to their low activation energy. The presence of π-π interactions can also guide the direction of molecular collisions to form H-bonds. Building upon this concept, we have successfully synthesized a series of HOF structures using a ball-milling method (Fig. 6(c)), following a topologically predicted assembly approach [66]. This method allows for lattice-based HOF preparation with minimal reliance on solvent-assisted synthesis. The stability of the frameworks was effectively enhanced by eliminating solvents in the self-assembly process.
Moreover, the existence of a large number of hydrogen donor/acceptor groups (such as hydroxyl, amine, and pyrazole) in HOFs allowed them to bind with various exogenous species to fabricate HOF-based derivatives. For example, by adding Pd precursors in the reaction mixture, a series of HOF-based composites, denoted as Pd@HOFs, were synthesized through a one-pot mechanosynthesis method [66]. The highly ordered HOF matrix not only acted as a surfactant to prevent nanoparticles from aggregating, but it also served as a porous substrate integrating various functional groups that enhanced mass transfer. The one-pot ball-milling synthesis method we developed is featured by its simplicity, cost-effectiveness, efficiency, and ease of obtaining nano morphs. This method also exhibited a certain degree of universality for different HOFs and scalability for production.
As shown above, various strategies have been utilized to synthesize stable HOFs with unique properties for different applications. As stable HOFs obtained using different methods may exhibit different structure features and properties, it is crucial to select the appropriate synthetic method for HOFs of interest. For instance, the adoption of π-π stacking may facilitate the construction of stable HOFs with catalytic capabilities, as π-π stacking can effectively induce charge transfer. Stable HOFs with charge-assisted H-bonds are suitable for gas storage and separation, leveraging their ionic channels [68]. Highly interpenetrated and chemically cross-linked stable HOFs can take advantage of the pore segmentation resulting from these strategies and also find application in gas storage and separation. Mechanical synthesis proves to be instrumental in fabricating nanosized HOFs tailored for biomedical applications. The careful selection of these strategies can lead to stale HOFs with desirable structures and properties for target applications.
In addition to these reported methods, researchers are actively exploring new synthetic strategies to craft stable HOFs with tailored properties for diverse applications.
The production of renewable fuels from solar energy and abundant resources, such as water and carbon dioxide, through photocatalytic reactions is considered a promising strategy to address the climate challenge adequately [69,70]. Photocatalytic systems based on porous materials have been studied to convert solar energy into hydrogen and other solar fuels. MOFs are common porous materials used for photocatalysis. However, the relatively low conductivity of MOFs requires the selection of suitable sacrificial agents. The modification of band positions by selecting appropriate linkers may be a way to improve the photocatalytic performance of porous materials, as exemplified by the recent development of COFs photocatalysts [71][72][73][74][75][76][77]. COFs can be viewed as pure linker frameworks, and one can tune band edges and porosity of COFs for a chosen application by selecting the appropriate linkers. Nevertheless, the harsh synthesis conditions of COFs limit their large-scale industrial production.
To this end, our group has analyzed how the preparation method could affect the structural properties and catalytic activity of HOFs. Based on the structure-activity relationship established, we have been optimizing the preparation method of porous HOFs by adjusting catalyst loading and morphology. In 2021, we combined metal catalytic sites with photosensitizers and investigated different metals to increase the stability of the framework and improve the CO 2 reduction activity (Fig. 7(a)) [78]. When using the designed HOFs as the catalysts, we determined that CO is the only product of the reaction through gas chromatography and ion chromatography. Among them, PFC-72-Co showed the best performance (14.7 μmol•g -1 •h -1 ), 1.5 times higher than PFC-73-Ni (9.8 μmol•g -1 •h -1 ) and 3 times higher than PFC-73-Cu (4.4 μmol•g -1 •h -1 ) times (Fig. 7(b)).
In addition, the performance of a photocatalyst depends on the photosensitizer's light-trapping ability and the charge transfer efficiency between the photosensitizer and the catalyst. Powder catalysts have poor visible light utilization due to aggregation and, thus, low photocatalytic efficiency. To tackle this problem, we synthesized a non-homogeneous structure by integrating Cu 2 O with a new porphyrin HOF, PFC-45 [79]. The heterogeneous ptype Cu 2 O and n-type HOF network showed higher charge separation efficiency. An efficient thin-film photocatalyst (PFC45/Cu 2 O@CP) with this inhomogeneous structure was developed using electrophoresis deposition (EPD) technology (Figs. 8(a Furthermore, inspired by the natural polystyrene bioprocess, we considered integrating a sufficient number of photosensitizers and an appropriate number of catalytic centers in one multiphase catalyst. This biomimetic multiphase catalyst was synthesized by self-assembling metalloporphyrin monomers into HOFs, in which the ratio of photosensitizer to catalytic centers can be adjusted by changing the percentage of metalloporphyrin centers in this prototype structure (Fig. 8(c)). The combination of experimental and computational results showed that changing the metalloporphyrin content not only achieved the fine-tuning of the photosensitizer/catalyst ratio but also significantly changed the microenvironment (e.g., electron density, substrate-skeleton interaction, and redox potential) and charge separation efficiency around the active center (Fig. 8(d)) [80].
Photocatalytic hydrogen production. Photocatalytic hydrogen production is considered a viable strategy for effectively using solar energy to solve the growing environmental and energy problems. With ordered structures, tunable pore sizes, and large specific surface areas, HOFs integrated with photoactive moieties are excellent photocatalysts for this application. The well-defined structures of HOFs can also facilitate studying structure-property relationships for these materials, which may provide insights into the photocatalytic mechanisms of HOF-catalyzed hydrogen production.
For this purpose, we integrated a photoactive graphitic carbon nitride (C 3 N 4 ) part in a HOF structure (PFC-42) with high porosity and crystallinity (Fig. 9 Conjugated organic photocatalysts generally exhibit broader light absorption but often suffer from relatively low apparent quantum yield (AQY). The low AQY may be attributed to the strong Coulomb attraction between positive and negative charges generated by organic semiconductors under irradiation, characterized by high exciton binding energies (typically > 0.1 eV). The high exciton binding energy means excitons must diffuse to the semiconductor surface to dissociate into carriers. However, most organic semiconductors have short exciton diffusion lengths (typically 5-10 nm), resulting in higher recombination rates and poor exciton dissociation [82,83].
In 2023, Zhu et al. employed transient spectroscopic methods to investigate the effect of micropores on exciton behavior [84]. Their method combines visible-mid-infrared femtosecond transient absorption spectroscopy (TAS) and time-correlated single-photon counting (TCSPC), which enabled them to study how the exciton transfer path of HOF-H 4 TBAPy was affected by its 1D micropore channels. In addition, the impact of the internal active adsorption region was further investigated using crystal engineering, specifically by controlling the length of the 1D channel. They also performed first-principles calculations and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy to study the reaction sites in the channels of the HOF. By controlling the one-dimensional channel length (≤ 0.59 μm), they found that micropore-confined excitons played a dominant role in photocatalysis and obtained a significantly enhanced H 2 evolution rate of 358 mmol•h -1 •g -1 (537 μmol•h -1 ; Fig. 9(g)).
Photothermal therapy (PTT) is an effective cancer treatment method that utilizes light-absorbing materials to convert nearinfrared (NIR) light energy into heat. This localized heat generation selectively eradicates cancer cells while minimizing damage to healthy tissue. PTT has gained significant attention in biomedical applications due to its minimally invasive nature. Although chemotherapy is a widely used and relatively reliable cancer treatment, mitigating its side effects is crucial. The combination of chemotherapy and PTT holds promising potential due to their synergistic effect, which enables a reduced dosage of chemotherapeutic agents to be effective and mitigates their associated adverse effects [85][86][87][88][89][90][91]. Hence, developing multifunctional biocompatible and biodegradable nanoplatforms integrating chemotherapy and thermotherapy holds significant potential for clinical cancer treatment. Photodynamic therapy (PDT) is an oncological treatment that has great potential due to its spatio-temporal specificity and non-invasive nature. PDT kills tumor cells directly by using reactive oxygen species and also induces an anti-tumor immune response through immune action.
With this objective in mind, in 2020, we pursued the integration of porphyrin photosensitizers as porous backbones and commercial bactericides as counterion (QA ions) into the structure [92]. PFC-33 demonstrated ion-responsive release behavior in diverse physiological environments, resulting in synergistic photodynamic and chemical antimicrobial efficacy. During membrane fabrication, the unbound carboxyl groups on the HOF surface enable precise control over the interfacial interactions between PFC-33 and the polymer matrix. Consequently, the poly-HOF membranes achieved excellent stability, desirable flexibility, and high permeability, exhibiting high efficacy in inhibiting E. coli growth (Fig. 10(a)). Moreover, the photo-responsive nature of HOFs allows for preparing wearable items. Li et al. reported the preparation of broadspectrum antimicrobial nanofibers using electrospinning, which incorporated a photoactive HOF consisting of rod-shaped nanocrystals measuring approximately 60 nm in length [93]. The resulting HOF@PVDF-HF nanofibers exhibited excellent tensile strength and breathability, protecting the HOF nanocrystals from acid and alkali corrosion (Fig. 10(b)). A series of nanofibers were prepared to optimize the efficiency of singlet oxygen ( 1 O 2 ) generation, incorporating varying amounts and types of HOF nanocrystals. It was found that the nanofibers containing 0.5 wt.% HOF-101-F@PVDF-HFP demonstrated the highest efficiency in 1 O 2 generation, exhibiting an enhancement of nearly two times compared to the HOF-101-F microcrystalline powder. The HOF@PVDF-HFP nanofibers effectively eliminated various pathogens, including viruses, bacteria, and fungi, within 30 min under ambient light conditions.
Near-infrared light therapy is widely recognized as highly effective; however, finding materials that emit near-infrared light, particularly framework materials, is challenging. With the goal of developing such materials, in 2021, we synthesized the first core-shell heterostructure up-conversion nanoparticles (UCNPs) and HOFs using a "bottle-around-ship" strategy combined with a stepwise ligand grafting approach [94]. The crystalline porous network can maintain a persistent radical state when exposed to visible light irradiation [95][96][97], demonstrating photothermal and photodynamic capabilities (Fig. 11(a)). Specifically, we selected B-NaYF4: Yb, Er UCNPs with an emission trap overlapping with the PFC-55 excitation wavelength. These UCNP materials were used to create a core-shell structure with PFC-55, enabling the utilization of near-infrared light energy for resonant energy transfer (RET) processes. This approach prevents the independent nucleation of physical mixtures and yields a uniform core-shell structure known as UCNPs@PFC-55. The core-shell heterogeneous structure facilitated the up-conversion of nearinfrared light (980 nm) into the visible region (540 and 653 nm) by the UCNPs "core", capable of deep tissue penetration (Fig. 11(b)) [98,99]. Subsequently, the PFC-55 "shell" is excited, leading to a notable photothermal effect and the generation of 1 Compared with coordinate and covalent bonds, hydrogenbonding interactions are intrinsically more flexible, weaker, highly reversible, and of low directionality, which endow HOFs with many unique advantages such as good solution processability, mild synthesis conditions, and multiple responsiveness. Besides, since HOFs are metal-free, the underlying harmful effect of metal ions on biological settings could be circumvented. These unique characteristics provide HOFs with great potential as a tunable platform for constructing multi-functional materials that are urgently needed for biomedical applications. For example, Falcaro et al. [101] have reported a biocompatible HOF, BioHOF-1, that can readily encapsulate two native enzymes and keep them active beyond biological conditions. More importantly, the strength of Hbonding spanned a large range in these HOFs. Relatively weak hydrogen bonding is more vulnerable to thermal stimulus. Thus, manipulation of the overall crosslinking force in HOFs can be realized by properly introducing multiple types of hydrogen bonds with different bonding strengths (i.e., hierarchical hydrogen bonds). Given these properties, HOFs have the potential to serve as a novel artificial exoskeleton for living cells, providing them with robust protection against severe chemical and physical lethal stressors, and showing the possibility of spatiotemporally controllable degradation upon NIR-II laser irradiation.
In 2022, Qu et al. [102] presented a new way to encapsulate neural stem cells (NSCs) by using HOFs to overcome the common causes of low therapeutic efficacy during NSC transplantation, including (1) loss of fundamental stem cell properties, "stemness", before transplantation, (2) cytomembrane damage during transplantation, and (3) apoptosis due to oxidative stress after transplantation. Porous carbon nanospheres (PCNs) were doped into the HOF shell during the process of mineralization to endow the cellular exoskeletons with hierarchical hydrogen bonds and the ability to resist oxidative stress due to the catalase and superoxide dismutase-like activities of PCN. Under NIR-II irradiation, thermal-responsive hydrogen bonds dissociated to release NSCs. Stereotactic transplanting encapsulated NSC into the brain of an Alzheimer's disease (AD) mouse model further verified that their design can enhance NSC viability, promote neurogenesis, and ameliorate cognitive impairment.
The activity of some enzymes relies on light-harvesting cofactors located in the active site. These cofactors facilitate the transfer of electrons or protons during irradiation, leading to complex biotransformation processes. The molecules that form the structure are interconnected, which can alter the internal electric field and energy gap. Furthermore, an extended π-π conjugated system likely enhances electron transfer. It suggests that conjugated crystal systems with a crystalline structure have greater photosensitivity than monomers, which is supported by the observed increase in photocurrent density during switching cycles. Flexible porous framework materials with adjustable structures, like HOFs, hold promise for advancing photo-responsive enzymes [103,104].
Considering this, Chen et al. [105] reported the pore environment-dependent, photo-responsive oxidase activity in three isostructural HOF nanozyme (Bovine albumin, BSA). They first sought out a series of photo-active carboxylate tectons suitable for the linkage into a HOF with an explicit structure and identified the tecons to have the best light-harvesting ability using density functional theory (DFT) calculation (Figs. 12(a) and 12(b)). According to the theoretical predictions, three photo-responsive isostructural HOF nanozymes possessed similar band gaps and generated comparable reactive oxygen species (ROS) under visible light irradiation. Remarkably, the photo-responsive oxidase activity, commonly considered ROS-dependent, drastically differed in these three HOFs. This variation in oxidase activity was demonstrated to be associated with the substrate-pore interaction, reminiscent of the binding effect of the native enzyme pocket that mediates the biocatalysis.
Photochromic materials are intelligent substances that alter their appearance or emit colors in response to external stimuli. These materials hold great potential for applications in anticounterfeiting measures. However, the majority of these materials demonstrate two-color transitions, low-contrast emission, or prolonged transition periods, rendering them impractical for realworld applications. HOFs with flexible framework structures exhibit superior responsiveness to external stimuli compared to COFs and MOFs. This characteristic positions HOFs as promising candidates in the field of photochromic materials.
Yang et al. [106] introduced a novel method involving the combination of a widely-used photochromic molecule, spiro pyran (SP), with HOFs (Fig. 13(a)). This approach enabled the reversible switching of SP in solid states and demonstrated dynamic displays of encrypted information. The composite system offers several advantages: (1) it exhibited diverse dynamic fluorescence emission and visible colors that are regulated by high-contrast ultraviolet radiation and can be reversibly converted; (2) these behavioral changes can be easily achieved through simple UV illumination; and (3) in contrast to prior studies, this work not only demonstrated dynamic fluorescence emission but also revealed dynamic information during the decryption process (Fig. 13(b)).
Ultralong organic phosphorescent (UOP) materials without any metal species exhibit significant potential for applications in optical technologies and biological imaging, owing to their low cost and biocompatibility. Nevertheless, preparing new UOP materials with extended luminous lifetimes and high photoluminescence quantum yields (PLQYs) remains a challenge [107]. Our group employed supramolecular self-assembly to combine two organic molecules, namely, the high PLQY compound 1,4-phenylene diboric acid (PBA) and the long-lived isophthalic acid (IPA), resulting in the formation of two crystalline hydrogen-bonded organic chains named PBA-IPA1 and PBA-IPA2 (Fig. 13(c)). PBA-IPA2 exhibited significantly enhanced phosphorescent lifetime (1.59 s) and PLQY (15.72%) compared to PBA-IPA1, attributed to the triplet-triplet energy transfer between the two components, further supported by computational studies.
The resulting material holds potential for applications in areas such as information encryption and fingerprint identification, offering a novel approach to designing UOP materials with practical uses (Fig. 13(d)).
Achieving simultaneous multiple functions in a single material has been a significant challenge, as individual functions are often difficult to correlate. Consequently, developing a single organic cocrystal/HOF material with multiple functions has been scarcely explored, despite the crucial importance of these multifunctional properties for practical applications. For instance, a material capable of simultaneously conducting electrons and protons could find applications in various fields, including organic electrochemical transistors, batteries, light-emitting electrochemical cells, chemical sensors, neuromorphic modules, bioelectronic probes, and ion pumps [108].
Recently, Zhang et al. [109] reported a 2D HOF denoted as HOF-FJU-36, based on a donor-acceptor (D-A) π-π stacking architecture (Fig. 14(a)). The framework involved the zwitterionic acceptor 1,1'-bis(3carboxybenzyl)-4,4'-bipyridinium (H 2 L 2 +
) and the donor 2,7-naphthalene disulfonate (NDS-2). Three water molecules were positioned within the channels, establishing hydrogen bonding interactions with acidic species, and contributing to forming a 3D framework. π-π interactions along a axis and a continuous hydrogen bonding chain along the b axis served as electron and proton transfer pathways, respectively (Fig. 14(c)). Upon irradiation with 405 nm light, the photogenerated radicals confer photo-switchable electron and proton conductivity to HOF-FJU-36 through coupled electron-proton transfer (Fig. 14(b)). The mechanism behind the irradiation-induced switchable conductivity has been elucidated through single-crystal X-ray diffraction (SC-XRD) analyses, X-ray photoelectron spectroscopy (XPS), transient absorption spectra, and density functional theory calculations (Figs. 14(d)-14(i)).
The unique dynamics and versatile applications of flexible hydrogen-bonded organic frameworks (FHOFs) have garnered significant attention. However, to mitigate potential issues with framework stability resulted from the relatively fragile nature of hydrogen bonds, most previous studies have focused on employing various strategies to construct robust and rigid HOFs [110]. These robust/rigid HOFs can maintain their original porous structures without undergoing any changes when exposed to external stimuli. In contrast, FHOFs are characterized as having the ability to undergo reversible structural transformations in response to external stimuli while preserving their crystalline nature [35,50,[111][112][113]. Despite the greater challenges in synthesizing stable FHOFs, their dynamic behaviors gradually garner more attention from the scientific community. Generally, at the very least, FHOFs should only lose the long-range order of their frameworks without transitioning into amorphous states throughout the entire stimuli-responsive process [114,115]. To induce reversible stimuli-responsive motions, FHOFs are typically constructed using flexible organic building blocks and weak hydrogen bonds. These design principles give rise to unique properties that are challenging to achieve in robust frameworks. It is worth noting that FHOFs generally exhibit a certain degree of stability, and their structures can undergo reversible transformations in specific environments while maintaining relative stability before and after the transformation. The reversible structural transformations of FHOFs, accompanied by changes in pore sizes and shapes in response to various factors such as guest molecules, temperature, and mechanical pressure, confer significant advantages in diverse applications. These applications include gas separation, luminescent sensors [116], host-guest chemistry [117], memory devices [118], and others. Synergistic photo-and thermal-responses. Compared with coordinate and covalent bonds, hydrogen-bonding interactions are intrinsically more flexible, weaker, highly reversible, and of low directionality, which endow HOFs with many unique advantages such as good solution processability, mild synthesis conditions, and multiple responsiveness. The flexibility inherent in the HOF framework can result in the distortion of molecular chains within the building unit region when exposed to external thermal stimuli, thus altering the configuration of the HOF [68]. Consequently, this change in configuration can impact the electron transfer process within the HOF, subsequently influencing its luminescence performance. For example, Chi et al. developed the first example of a FHOF with local dynamics (named 8PZ) for adaptive guest accommodation through incorporating soft ethylester chains [110]. In the presence of various external stimuli such as solvents and temperature, local motions of ethyl-ester chains could occur, including in-plane and out-of-plane motions, which can efficiently regulate the pore size of 8PZ without significant changes in cell volumes and molecular assembling forms. Moreover, through the local dynamics, 8PZ can adapt to a series of 3-alkylthiophenes with large-scale alkyl-chain-length variation (Figs. 15(d) and 15(e)). Ten host-guest cocrystals suitable for SXRD analyses were further produced, which presented programmable temperature-dependent luminescence properties and showed great potential for microscale luminescent thermal alarms and multiple information encryption with logic programming (Fig. 15(b)). As a multifunctional smart platform, the FHOF, 8PZ, with local dynamics, is also promising for applications in sensing, catalysis, biomedical imaging, optoelectronic devices, and many others. The employment of FHOFs with local dynamics as hosts in host-guest cocrystals should also provide a valuable strategy for the preparations of functional cocrystals. This work not only deepened our understanding of the relationship between framework structures and flexibilities of HOFs but also provided a hopeful avenue to engineer future multifunctional FHOFs with enriched applications.
Recently, Zhang et al. [119] reported the first smart-responsive HOF heterostructure with multiple spatial-resolved emission modes as a covert photonic security platform via differentiated design on high-electronegative atoms. HOF heterostructures were prepared by integrating different HOFs into a single microwire based on a hydrogen-bond-assisted epitaxial growth procedure. Adopted HOFs with different substitution positions of highelectronegative atoms exhibited distinct responsive characters, which endowed HOF heterostructures with both the thermochromism via the framework transformation and the acidichromism via the protonation effect, leading to multiple emission modes. Dual-stimuli-controlled emission modes and spatial-resolved emission behavior constituted a fingerprint of the heterostructure, which allowed for realizing smart-responsive photonic barcodes with multiple convert states, further demonstrating the dynamic coding capability and enhanced security as anticounterfeiting labels.
These results provide a promising route for the functionoriented design of smart-responsive HOF heterosystem, which may serve as a novel platform for optical data recording and information encryption.
Synergistic photo-and pressure-responses. Bionic sensors have played a significant role in the advancement of smart robots, medical equipment, and flexible wearable devices. The luminescent pressure-acoustic bimodal sensor can be regarded as an exceptional multifunctional integrated bionic device. Owing to its flexible and porous properties, HOF shows promising prospects for development in wearable devices and bionic devices.
Recently, Yan et al. [120] successfully synthesized flexible and elastic pressure-acoustic bimodal sensors, denoted as HOF-TTA@MF (1 and 2) (Fig. 16 In 2021, Chi et al. [116] demonstrated a dynamic 2D woven HOF with permanent porosity constructed through the interlocking of 1D strands. The 1D strands with holes were assembled by O-H•••O hydrogen bonds with the changeful feature, into which X-shaped organic building blocks of orthogonal 1D strands can be interlocked. Due to the existence of the changeful hydrogen bonds, the angle between warps and wefts can be switched between 90.0° and 82.0° when responding to ethyl acetate (EA) and methanol (MeOH) vapors (Figs. 17(c), 17(e), and 17(f)), respectively, revealing the exceptional dynamics of the molecular woven structure. During the reversible structural transformations, the woven HOF also exhibited large-scale elasticity switching and high-contrast stimuli-responsive luminescence behaviors.
Despite the growing research interest in HOFs, their potential in electrochemical applications was limited by the weak nature of the hydrogen bonds, which are susceptible to dissociation in the solution, compromising the structural integrity of HOFs [122].
In 2021, Wang et al. demonstrated that the solution stability of HOFs may be improved by designing and introducing multisite hydrogen bonding within HOFs (Fig. 18(a)) [123]. Using this strategy, 2D molecular sheets were prepared from diamino triazole linkers for the first time. This solution-stable HOF exhibited an excellent electrochemical performance for Na + ion storage (Fig. 18(b)). It enabled an exceptional cycle life of > 10,000 cycles at 1 A•g -1 , which is far superior to most other organic electrode materials (Figs. 18(c) and 18(d)). Theoretical simulations indicated that the activation barrier for the intralayer or interlayer diffusion of Na + within the organic frameworks was small. Recently, to study the selective two-electron redox reactions in acidic media, we screened 32 different metalloporphyrin 2-eoxygen reduction reactions (ORRs) against H 2 O 2 using highthroughput density flooding calculations [124]. Among them, cobalt porphyrins have the best activity and selectivity with theoretical overpotentials as low as 0.04 V. Guided by the theoretical predictions, we prepared hydrogen-bonded cobalt porphyrin skeletons through the self-assembly of TCPP-Co in solution. PFC-72-Co was characterized by high structural crystallinity, large specific surface area, and abundant catalytic centers. This HOF can efficiently and consistently produce H 2 O 2 in 0.1 M HClO 4 with an onset potential of 0.68 V. The H 2 O 2 selectivity is > 90% within a wide potential window. The TOF value of 10.9 s -1 at 0.55 V is not only much better than that of Reproduced with permission from Ref. [116], © Elsevier Inc. 2021. organic or inorganic alloys, but it is also better than the state-ofthe-art Pt/Pd-Hg alloy.
Electrochromic (EC) materials are [125,126] derived from metal oxides [127,128], Violagen and its analogs [129], MOFs, and COFs [130], which have a wide range of applications in bright windows, information storage, electronic displays, dynamic mirrors, etc. The unique properties of HOFs, such as easy modification, adjustable structure, and high porosity, can help achieve the regulation of electrochromism at the atomic level. These characteristics can speed up the electron transmission rate, improving electronic transmission performance. Therefore, HOFs have good prospects in the field of electrochromism.
HOFs can form charged particles during protonation or deprotonation due to the extensive presence of proton and hydrogen donor/acceptor sites in the structure, which inspired us to apply electrophoresis deposition (EPD) to prepare HOF films. In 2020, using the EPD method, we successfully deposited a high porosity HOF, PFC-1, on transparent fluorine-doped tin oxide (FTO) glass as the electrochromic bright window (Fig. 19(a) and 19(b)) [131]. The resulting film had a uniform morphology, dense surface, and high crystallinity, and the method was equally applicable to other HOFs and substrates. The PFC-1 films prepared on FTO glass had reversible electrochromic properties, with the color changing from yellow to blue-violet and the transmittance decreasing from 75% to 25%. In addition, due to the presence of unbound carboxylic acids at structural defects and particle surfaces, the films can be further modified with Fe ions to achieve multi-state electrochromic, demonstrating the unique tunability of HOF for specific needs. We then used an efficient and low-cost electrostatic spray deposition (ESD) method to directly prepare large-area HOF films (30 cm × 30 cm) on unmodulated conductive substrates (Fig. 19(d)). Combining the ESD with a templating method, HOF membranes can be easily fabricated in various patterns, including deer-shaped and horseshaped membranes (Fig. 19(f)). The obtained film had excellent electrochromic properties, achieved multi-color changes from yellow to green and purple, and can be dual-band tuned at 550 and 830 nm. PFC-1 films can change color quickly (within 10 s) thanks to the inherent channels of the HOF and the additional film porosity created by ESD [132]. Furthermore, we constructed large-area patterned electrochromic devices based on the above films to demonstrate their potential for practical applications.
In recent years, photoelectrochemical (PEC) detection has emerged as an innovative biosensing technique widely employed for trace analysis due to its ultrahigh sensitivity, low background noise, and good reproducibility compared to traditional detection methods [133]. In a typical detection process, the photoactive material serves as both a functional layer for photoelectron generation and an identification layer for the analyte. Unlike transition metal-based photoelectric semiconductor materials, such as ZnO and Cu 2 O, which only provide surface chemical recognition, analogous HOF-based photoelectric sensors offer additional sensing capabilities due to their inherent porosity. Furthermore, the photoactivity, semi-conductivity, and ordered nanopores of porous molecular traps can facilitate photo-induced electron generation and transport and serve as both a size and site recognition layer, enabling selective detection of target analytes in the presence of interfering substances [133].
In 2022, Xiao et al. [134] utilized aggregation-induced enhanced emission (AIEE)-active H 4 TBAPy as a building block to synthesize a novel HOF-based electrochemiluminescence (ECL) material called Py-HOF (Fig. 20(b)). They introduced a pyrene-based hydrogen-bonded organic framework (Py-HOF) with outstanding ECL performance, which was prepared by using 1,3,6,8-tetrakis (pbenzoic acid) pyrene (H 4 TBAPy) with an AIEE property as the building block, and exhibited a stronger ECL emission than that of the H 4 TBAPy monomer. H 4 TBAPy aggregates, the low-porosity Py-HOF-210 °C and Py-HOF-180 °C. We have coined the term "the porosity and aggregation-induced enhanced ECL (PAIE-ECL)" for this intriguing phenomenon. The Py-HOF displayed superb and stable ECL intensity, not only because luminophore H 4 TBAPy was assembled into the Py-HOF via four pairs of O-H•••O hydrogen bonds, which constrained the intramolecular movements to reduce nonradiative transition, but also because the H 4 TBAPy in Py-HOF was stacked in a slipped face-to-face mode to form J-aggregates that benefited the ECL enhancement. Additionally, the high porosity of Py-HOF enabled the rapid transfer of ions, electrons, and co-reactants, enhancing the utilization of luminophores. Due to its excellent ECL properties, Py-HOF served as an ECL probe. It was integrated with a 3D DNA nanomachine amplification strategy to fabricate a "switch" ECL sensor, enabling ultra-sensitive detection of miRNA-141 (Fig. 20(a)).
In 2022, Li et al successfully encapsulated ultrafine sub-1 nm AgNPs within HOFs using an environmentally friendly photoreduction synthesis method conducted under ambient conditions without needing harmful chemicals, stringent conditions, or cumbersome operations (Fig. 20(c)) [135]. These AgNPs@HOFs demonstrated not only enhanced photocurrent compared to pristine HOFs, selected MOFs, and semiconductors, but they can also selectively enrich mustard gas mimics through the size exclusion effect. The photo-electrochemistry (PEC) sensor demonstrated a distinct photocurrent response to 13 diverse mustard gas mimics. The combined size exclusion effect and specific recognition of Ag(I) and -Cl on these mimics contributed to the high selectivity of the AgNPs@HOF-modified PEC sensor, which achieved a CEES detection limit of 15.8 nmol•L -1 and encompassed a broad linear range from 20 to 400 nmol•L -1 . The straightforward preparation method described in this study could be employed to obtain other types of metal nanoparticles (e.g., Au, Pt, Pd NPs) encapsulated within HOFs, thereby paving the way for the advancement of highly selective, sensitive, and portable detection devices based on PEC sensing for various toxic chemical warfare agents (CWAs) like mustard gas and nerve agents.
Recently, a facile bottom-up growth method was also reported to achieve a high yield (89%) of large-area (up to 23,500 µm 2 ) porphyrin tablets with controllable thicknesses ranging from 0.298 to 2.407 µm [136]. The tablets exhibited a high density of 2D hydrogen bonding in their structure. The DAT moieties on the porphyrin molecules facilitated the formation of complementary hydrogen bonds between the structures and acted as recognition sites for the selective adsorption of CO 2 in the resulting porous HOF materials. FDU-HOF-2 can be grown and deposited directly onto various substrates, such as silica, carbon, and metal oxides, through in situ self-assembly in formic acid (Fig. 21(a)). As proof of concept, we fabricated label-free PEC sensors for CO 2 detection by depositing FDU-HOF-2 onto screen-printed electrodes (Fig. 21(g)). The resulting PEC sensor operated in a signal-off mode, demonstrating a low CO 2 detection limit of 2.3 ppm, reusability for at least 30 cycles, and long-term operational stability lasting at least 30 days.
In this review, we provided an overview of recent research progress made toward developing stable HOFs, focusing on five prominent synthetic strategies: (1) π-π stacking, (2) interpenetration, (3) chemical crosslinking, (4) charge-assisted Hbonds, and (5) mechanical synthesis. A large number of stable HOFs with diverse structures have been synthesized using these strategies, and they have been studied for various applications. Despite the limited active sites in HOFs compared to MOFs, HOFs have many unique properties, such as their ability to recrystallize and self-repair, which can facilitate their recyclability and reduce material consumption. Additionally, the weaker intermolecular interaction forces between HOF building blocks give HOF the potential to be a responsive material to external stimuli. For example, by incorporating suitable motifs, HOFs can gain intrinsic photo-responsive abilities, and a suitable topology with π-π interactions can further facilitate the transmission of photocurrent. Moreover, the metal-free nature of HOFs makes them attractive materials for biomedical applications.
Thanks to the improved stability of HOFs and their unique properties, the function of HOFs has also been extended significantly over the past decade. Taking advantage of the photoactivities and photo-responses of stable HOFs, researchers have utilized HOFs for photocatalysis, photocatalytic hydrogen production, and photodynamic and photothermal therapy. Some HOFs also demonstrated biomimetic photo-responsive enzymatic activities, or can change their color or electron/photon conductivity in response to external stimuli, expanding their applications in stimuli-responsive biocatalysis, photochromic devices, sensing, and others. In addition to stable HOFs with rigid structures, stable FHOFs with flexible structures have also been investigated. These FHOFs can undergo a reversible structural transformation in response to one or two external stimuli, enabling their synergistic response to photo-and one other external stimuli, including temperature, pressure, and chemical stimuli. Furthermore, by improving the stability of HOFs using the strategies mentioned above, HOFs have also found
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