Chongxiong Dun,Kun Ling,Zn Zhng,Jingjing Li,Ting Chn,Dofi Lv,Lio Li,L Kng,Ki Wng,Hn Hu,Hongxi Xi,＊＊

a School of Materials Science and Hydrogen Engineering,Foshan University,Foshan,528231,China

b School of Chemistry and Chemical Engineering,South China University of Technology,Guangzhou,510640,China

c State Key Laboratory of Heavy Oil Processing,College of Chemical Engineering,Institute of New Energy,China University of Petroleum(East China),Qingdao,266580,China

d School of Materials Science and Engineering,Xi'an University of Science and Technology,Xi'an,710054,China

e School of Electrical Engineering,Qingdao University,Qingdao,266061,China

Keywords:Metal–organic frameworks Nanoscale Hierarchically porous structure Synthesis strategies

ABSTRACT Nanoscale hierarchically porous metal–organic frameworks(NHP-MOFs)have received unprecedented attention in many fields owing to their integration of the strengths of nanoscale size(<1 μm)and hierarchical porous structure(micro-,meso-and/or macro-pores)of MOFs.This review focuses on recent advances in the main synthetic strategies for NHP-MOFs based on different metal ions(e.g.,Cu,Fe,Co,Zn,Al,Zr,and Cr),including the template method,composite technology,post-synthetic modification,in situ growth and the grind method.In addition,the mechanisms of synthesis,regulation techniques and the advantages and disadvantages of various methods are discussed.Finally,the challenges and prospects of the commercialisation of promising NHP-MOFs are also presented.The purpose of this review is to provide a road map for future design and development of NHP-MOFs for practical application.

1.Introduction

Metal–organic frameworks(MOFs)are an emerging class of porous crystalline materials that consist of organic ligands and inorganic building units(metal ions or clusters)[1].When compared with conventional porous materials(e.g.,zeolites,activated carbon,metal oxide,and polymer),MOFs have distinct advantages,such as high surface area,permanent porosity,and tunable functionality,making them promising candidates in various applications,such as adsorption/separation[2],drug delivery[3,4],conduction[5,6],sensing[7],and catalysis[8].Currently,over 80,000 MOFs have been reported to the Cambridge Structural Database(CCDC)[9].Despite their fascinating physico-chemical characteristics,most of the MOF crystals reported to date are of the order of micrometres(crystal size>1 μm)and their pore structure belong to micropores(pore size<2 nm)[10,11].The bulky crystal size increases the diffusion path of guest molecules to the interior,whereas the small pore aperture inherently hinders fast diffusion and mass transfer of reactants or products,resulting in a negative synergistic effect that severely limits their practical application,particularly those involving large molecules[12,13].As a result,developing an effective strategy to reduce crystal size and/or extend the pore size of conventional MOFs is essential[14].

To tackle the above issues,downsizing conventional MOFs to nanoscale in at least one dimension can shorten diffusion pathways of guest molecules,and extend external surface areas allowing accessible active sites to be exposed,thereby enabling numerous new potential applications[15,16].For example,nanoscale MOFs are preferred for drug delivery and biomedical imaging[17,18].In addition,when used as electrode materials for various batteries,nanoscale MOFs can boost electrolyte penetration to improve electrochemical performance[19].To date,two strategies for preparing nanoscale MOFs(N-MOFs,crystal size<1 μm)have been developed:bottom-up strategies(e.g.,reaction parameter-and coordination-assisted synthesis)and top-down strategies(e.g.,liquid exfoliation and salt-template confinement)[11].On the other hand,extending the pore sizes of microporous MOFs to a larger regime,including mesopore(2–50 nm)and even macropore(>50 nm)isan available route.Consequently,the formation of hierarchically porous MOFs(HP-MOFs)will not only keep the function of micropores,but also generate meso-or macro-pores across the microporous matrix.This is beneficial to the required accessibility/space toward guest molecules and minimizes diffusion resistance[14].To date,four major strategies for synthesizing HP-MOFs have been developed:(i)ligand-extension,(ii)template,(iii)defect,and(iv)the post-modification methods[20].Although N-MOFs and HP-MOFs have been extensively studied in recent years,the effect on improving diffusion and mass transfer is unsatisfactory because of unilateral improvements such as decreasing crystal size or introducing extended pores that are one-sided.

Fig.1.(a,b)SEM images and(c)N2 adsorption–desorption isotherms and pore size distribution curves(based on Barrett–Joyner–Halenda(BJH)analysis)of the NHPMOFs synthesized in IL/EG mixture.Reprinted with permission from Ref.[30].

Nanoscale hierarchically porous MOFs(NHP-MOFs)combine the advantages of nanoscale and hierarchically porous structure,thereby providing an original path to solve mass transfer issues.In practice,the nanoscaled crystal size and extended pore in NHP-MOFs have a synergistic effect in the diffusion and mass transfer of guest molecules,conferring material properties that are completely different from those of N-MOFs or HP-MOFs[21,22].Many NHP-MOFs based on various metal ions(e.g.,Cu,Fe,Co,Zn,Al,Zr,and Cr)have been synthesized using a variety of strategies,including the template method,composite technology,post-synthetic modification,in situ growth,and the grind method.These approaches have been successfully applied in preparing high-quality NHP-MOFs,with the crystal size and porosity of the resultant NHP-MOFs readily tailored by controlling appropriate parameters(e.g.,template type,concentration,reaction conditions)[23,24].There have been many reviews summarizing the preparation methods of N-MOFs and HP-MOFs[11,25,26].However,to the best of our knowledge,no special review has comprehensively summarized the selection and optimization of synthetic methods for preparing NHP-MOFs based on metal centres.Therefore it is timely to summarize the state-of-the-art work related to the main synthetic strategies of NHP-MOFs based on various metal ions(e.g.,Cu,Fe,Co,Zn,Al,Zr,and Cr).Furthermore,this review compares their synthesis mechanisms,regulation techniques,as well as the merits and demerits of different methods.Finally,challenges and outlook are suggested to help future research directions.

2.Different types of NHP-MOFs based on metal ions

2.1.Copper-based NHP-MOFs

Cu-BTC{Cu3(TMA)2(H2O)3?xH2O,where TMA is benzene-1,3,5-tricarboxylate}is a typical copper-based MOF that has been widelyinvestigated since 1999,wherein the crystal size is of micrometre scale(~10 μm)and pore structure belongs to the microporous regime(~0.86 nm)in conventional Cu-BTC[27,28].To date,many strategies have been developed to reduce the dimensions of conventional Cu-BTC down to the nanometer regime or to introduce mesopores or macropores,but only few advanced methods can solve both problems simultaneously.For example,Han et al.[29]reported the synthesis of nanoscale mesoporous Cu-BTC in the mixture of surfactant(N-ethyl perfluorooctylsulfonamide)and ionic liquids(ILs,1,1,3,3-tetramethylguanidine).The sizes of as-synthesized MOFs are 60–80 nm with mesopores of about 2–4 nm.The nanoscale and hierarchical pore of MOF crystals can be attributed to the introduced surfactant that plays dual roles(directing the crystal growth and as a template).At the same time,the ILs provide a tunable and friendly reaction environment.

Fig.2.SEM and TEM images of the nanoscale hierarchical porous Cu-BTC synthesized from solutions containing various molar concentrations of N,N-dimethyloctadecylamine.Reprinted with permission from Ref.[32].

Fig.3.Schematic of Cu-BTC-Mg-Al-LDH composites synthesis from an exfoliation-self-assembly route.Reprinted with permission from Ref.[35].

Recently,Zhang et al.[30]reported the synthesis of nanoscale Cu-BTC with a bimodal mesoporous structure(3.9 and 17–28 nm)in an IL/ethylene glycol(EG)mixture.As shown in Fig.1a,the as-synthesized Cu-BTC samples consist of nanoparticles with a diameter~5 nm and apparent mesoporous networks can be observed,with a pore diameter in the range of 2–30 nm(Fig.1b).The N2adsorption–desorption isotherm of the sample shows an intermediate mode of type I/IV,indicating the coexistence of micropores and mesopores(Fig.1c).The sample's pore size distribution curves show a bimodal mesoporous structure with pore size distributions centred at 3.9 and 16.5 nm,separately(Fig.1c).Furthermore,the large mesopore of nanoscaled Cu-BTC can be easily modified by varying the amount of EG from 17 to 28 nm.When compared to small mesopore sizes(<5 nm),large mesopores in MOFs exhibit superior diffusion and mass transfer performance in their applications[31].

Other than the ILs synthesis conditions,nanoscale hierarchically porous Cu-BTC can be prepared in organic solvents using a similar template strategy.Recently,Xi et al.[32]synthesized hierarchically porous Cu-BTC with a crystal diameter of about 100 nm using N,N-dimethyloctadecylamine as the template in water and ethanol.As shown in Fig.2,the resulting Cu-BTC samples are nanoscaled block-shaped particles with pores 20–100 nm in size between them,as opposed to conventional Cu-BTC with octahedral shapes.Organic solvents require a higher reaction temperature and pressure(90°C vs 30°C)than ILs[29],but the organic solvent conditions result in larger crystal size(~100 nm vs 60–80 nm)and a wide range of pore sizes from mesopores to macropores(20–100 nm vs 2–4 nm).

In addition to the surfactant,some nonmetallic oxide,metallic oxide,and polymers also are used as additives to regulate MOF properties(e.g.,size,porosity,and morphology)in special synthesis conditions(e.g.,ultrasound,microwave-assisted).The introduced surfactants are easily removed via washing,whereas these additives typically incorporate into MOF crystals to form composites that open up new possibilities in application[33].For example,Qiu et al.[34]reported the one-step preparation of nanoscale hierarchically porous Cu-BTC@SiO2core–-shell composites using the ultrasonic method at facile conditions within a short time.A transmission electron microscope(TEM)study showed that the Cu-BTC crystals had been coated with amorphous silica to form cubiform colloids with a core–shell structure.The composites have uniform particle sizes in the 200–400 nm range and a shell thickness ranging from 12 to 60 nm,and the hierarchically porous structure can be found between the Cu-BTC core and the silica shell.

Recently,Hwang et al.[35]reported an exfoliation-self-assembly route to synthesize Cu-BTC-Mg-Al-LDH composites.These are derived from Cu-BTC nanocrystals(~5–10 nm)and layered double hydroxide(LDH)with a mesoporous structure.As shown in Fig.3,the nanoscale Cu-BTC crystals can be uniformly anchored on the surface of Mg–Al-LDH nanosheets,resulting in the formation of nanoscale hierarchically porous MOF composites.Furthermore,the hybridization of Cu-BTC crystals and LDH nanosheets improves MOF porosity by forming mesoporous house-of-cards-type stacking structures and prevents MOF crystal aggregation[36].The as-synthesized Cu-BTC-Mg-Al-LDH composites exhibit better hydrostability and greater water absorptivity than conventional Cu-BTC.Li's group reported the synthesis of a series of nanoscale metal@MOF@ MCM-41 composites (e.g.,Cs-POM@MOF-199@MCM-41,C-POM@MOF-199@MCM-41)with hierarchical pores,and the resulting sample exhibits improved catalytic performance[37–39].

2.2.Iron-based NHP-MOFs

MIL-100(Fe)is one of the most extensively explored Fe-based MOFs in recent years because of its outstanding physicochemical properties,such as inherent hierarchical pores,lacking in vivo toxicity[40].Despite the presence of micropores(0.5–0.9 nm)and mesopores(2.5–2.9 nm)in conventional MIL-100(Fe),the crystal size is in the micrometre range(>5 μm)[41].As a result,the key to obtaining nanoscale hierarchically porous MIL-100(Fe)is to downsize the material from the micrometre to the nanometer regime.For example,Horcajada et al.[42]reported the synthesis of nanoscale hierarchically porous MIL-100(Fe)and their composites(denoted as hep_MIL-100(Fe))by modifying the MIL-100(Fe)external surface with heparin.The XRD result indicates that the characteristic peaks of hep_MIL-100(Fe)are similar to MIL-100(Fe),indicating that the introduction of heparin had no impact on MOF crystalline structure.The particle size(determined using dynamic light scattering(DLS))of pristine MIL-100(Fe)and hep_MIL-100(Fe)composites was 173±51 nm and 141±43 nm,respectively,confirming that the materials are nanoscale.The as-synthesized hep_MIL-100(Fe)materials have low toxicity and are effective at decreasing cell recognition and uptake during the early stages of incubation,giving them potential stealth properties.This result indicates that MOF composites can have improved properties because of their synergism effect when compared to pure MOFs[43].

Zhu et al.[44]reported the synthesis of nanoscale AgPd@MIL-100(Fe)composites with core–shell structure using a facileone-pot route.As shown in Fig.4,the bimetallic AgPd alloy NP core is coated with a uniform MIL-100(Fe)shell,and all AgPd@MIL-100(Fe)composites have well-defined core–shell nanospherical structures with crystal size ranging from 100(AgPd@MIL-100(Fe)_A)to 250 nm(AgPd@MIL-100(Fe)_C).In particular,the diameter of the AgPd NP cores of AgPd@MIL-100(Fe)decreased from 86 to 14 nm,while the shell thickness increased from 7 to 118 nm.These results suggest that by varying the amount of AgPd precursors,the crystal size of NHP-MOF composites can be tuned.Moreover,N2adsorption–desorption isotherm and pore size distribution results indicate that the resulting AgPd@MIL-100(Fe)_B and AgPd@MIL-100(Fe)_C have micropores(~0.9 nm)and mesopores(~2.2 nm).The as-synthesized AgPd@-MIL-100(Fe)composites exhibited improved catalytic activity for generating hydrogen from formic acid decomposition at room temperature due to the synergism effect of noble metal NPs and MOFs.

Fig.4.TEM images of the obtained(a,b)AgPd@MIL-100(Fe)_A,(c)AgPd@MIL-100(Fe)_B,(d)AgPd@MIL-100(Fe)_C.Reprinted with permission from Ref.[44].

The conventional MIL-100(Fe)has small mesopores(<5 nm),but its application is limited to some extent because of the small mesopores[30].To address this issue,Xi et al.[45]used the mixed-ligand method to synthesize nanoscaled MIL-100(Fe)with large mesopores and macropores via simultaneously introducing terephthalic acid(TPA)and p-benzoquinone.The large mesopores,which are primarily 40 nm in diameter,are caused by structural defects in crystals due to the introduction of TPA.The nanoscale MIL-100(Fe)can be attributed to the H3BTC molecules that were partially exchanged by TPA.The resulting nanoscale hierarchically porous MIL-100(Fe)showed significantly improved performance over conventional MIL-100(Fe)and zeolites used for toluene and p-xylene adsorption.In addition,other nanoscale hierarchically porous Fe-based MOFs and their composites,such as MIL-88(Fe),MIL-101(Fe)and NH2-MIL-101(Fe),have also been synthesized and show excellent performance[46–48].

2.3.Cobalt-based NHP-MOFs

Zeolitic imidazole frameworks-67(ZIF-67)is a representative of Cobased MOFs that has been widely investigated in recent years.Its crystal size is approximately 600 nm and the pore size is of micropores(~0.34 nm)[49].Therefore,studies for obtaining nanoscale hierarchically porous ZIF-67 are mainly focused on extending pore size from micropores to mesopores and/or macropores.Recently,Xi et al.[50]reported the rapid preparation of nanoscale hierarchically porous ZIF-67(NH-ZIF-67)crystals using an N,N-dimethyl-1,2-ethanediamine as a bifunctional modulator.As shown in Fig.5,on the one hand,the introduced N,N-dimethyl-1,2-ethanediamine enhanced the deprotonation degree of the 2-methylimidazole,resulting in the rapid growth of ZIF-67 with a crystal size below 200 nm,which is much smaller than conventional ZIF-67.On the other hand,the introduced N,N-dimethyl-1,2-ethanediamine acted as a modulator through self-assembly to form columnar aggregation,guiding the formation of mesopores with a diameter of 40 nm and macropores(>50 nm).When compared to their counterparts,the resulting NH-ZIF-67 demonstrated improved adsorption performance in the capture of toluene and malachite green.

Fig.5.Schematic of nanoscale hierarchically porous ZIF-67 synthesized with an organic amine as bifunctional modulator.Reprinted with permission from Ref.[50].

Fig.6.Schematic of the preparation of sandwich-like GS@ZIF-67 composites.Reprinted with permission from Ref.[56].

In addition,some nonmetallic oxides,metallic oxides and polymers usually loading on ZIF-67 to form nanoscale hierarchically porous ZIF-67 composites and show better properties than the single material[51,52].Zhang et al.[53]reported novel nanoscale hierarchically porous ZIF-67/carbon aerogels(CAs)composites using an in situ deposition method,in which the CAs with pore sizes ranging from 15 nm to 20 nm provide a significant number of active sites for the growth of ZIF-67 nanocrystals and ensure a high mass content ZIF-67 coating.Because of the abundance of oxygen functional groups on the surface of CAs that can adsorb Co2+and promote the nucleation of ZIF-67 nanocrystals[54,55],ZIF-67 with crystal sizes less than 500 nm are uniformly deposited on the surface of CAs.It should be pointed out that,however,the as-synthesized nanoscale hierarchically porous ZIF-67/CAs are only intermediate products to obtain Co3O4/CAs composite.

Recently,MOF-graphene composites have been widely investigated in the fields of supercapacitors and the environment.For example,Chen et al.[56]loaded ZIF-67 on two sides of physically exfoliated graphene nanosheets(GSs)at room temperature to synthesize sandwich-like GS@ZIF-67 composites,using an in situ method at room temperature without a binding agent.As shown in Fig.6,the carboxylic groups(-COOH)were introduced to the surface of GSs,and then a MOF precursor(Co2+)was adsorbed on the surface of the GSs because of the electrostatic effect.Subsequently,the ligand(2-methylimidazolate)and Co2+rapidly self-assemble on the surface of GSs as the heterogeneous crystal nucleation,resulting in the formation of sandwich-like GS@ZIF-67 composites with ZIF-67 uniformly coated on both sides of the GS.SEM and TEM images of GS@ZIF-67 composites showed that the crystal size of ZIF-67 was about 300 nm and hierarchical pores were observed among GSs and ZIF-67 nanocrystals.The as-synthesized nanoscale hierarchically porous GS@ZIF-67 composites showed excellent electrochemical activity toward glucose oxidation compared with the same ratio of a simple physical mixture of ZIF-67 and GSs.

Deep et al.[57]reported a simple one-pot method to synthesize ZIF-67/PEDOT composites(PEDOT,Poly(3,4-ethylene dioxythiophene)).SEM and TEM images showed that the ZIF-67 crystals with diameters in the range of a few hundred nanometers(100–500 nm)are visibly distributed in the PEDOT layers,and hierarchical pores can be observed between ZIF-67 nanocrystals and the PEDOT polymer.The results of type I/IV N2adsorption-desorption isotherms and pore size distribution curves(based on Barrett–Joyner–Halenda analysis)show that micropores and mesopores exist in ZIF-67/PEDOT composites.The resulting ZIF-67/PEDOT composites were used to build an all-solid-state symmetrical supercapacitor with high power density(200 W/kg)and energy density(~11 Wh/kg).In addition,Xiao et al.[58]described the synthesis of nanoscale hierarchically porous ZIF-67@LDH composites using ZIF-67 as a template.The crystal size of the as-synthesized ZIF-67@LDH is about 690 nm,and the mesopores are derived from the surface of ZIF-67 in ZIF-67/PEDOT composites.The crystal size of ZIF-67@LDH composites belongs to the nanoscale while ZIF-67/PEDOT composites are at the micrometre.This can be attributed to the carrier of PEDOT far outweighing LDH.As a result,selecting the appropriate size carrier is one accessible route to obtaining nanoscale MOF composites.Overall,most methods for creating nanoscale hierarchically porous MOF composites are not suitable for producing truly nanoscale crystals with sizes smaller than 200 nm.

Fig.7.(a)SEM,(b)TEM,and(c)HRTEM images of the nanoscale hierarchically porous Zn-MOF-74.Reprinted with permission from Ref.[60].

Fig.8.Schematic of the supramolecular template concept for synthesis of nanoscale hierarchically porous ZIF-8.Reprinted with permission from Ref.[65].

2.4.Zinc-based NHP-MOFs

Zn-MOF-74 with a formula of Zn2(DHBDC)?(guest)n(DHBDC=2,5-dihydroxy-1,4-benzenedicarboxylate)is a representative material of zinc-based MOFs that exhibits a hierarchical microporous and mesoporous structure[59].However,the mesopores of conventional Zn-MOF-74 are small than 5 nm,which is unfavourable for diffusion and mass transfer of large guest molecules[31].Therefore,the extension of Zn-MOF-74 pore widths to large mesopores(>10 nm)is of great interest.Recently,Dai et al.[60]reported the rapid preparation of nanoscale hierarchically porous Zn-MOF-74 with large mesopores at room temperature using a template-free method.The SEM image in Fig.7a shows that Zn-MOF-74 is made of nanoparticles with a diameter of about 10 nm,and the apparent voids surrounded by the nanoparticle walls confirm the presence of mesoporous structures with widths ranging from 5 to 20 nm(Fig.7b).The existence of nanoscale Zn-MOF-74 particles and large mesopores was also supported by high-resolution TEM(HRTEM)analysis,as shown in Fig.7c.Moreover,the pore size distribution results(based on NLDFT analysis)further confirm the mesopores exceeding 15 nm.In addition,the surface shape and porosity of the nanoscale hierarchically porous Zn-MOF-74 can be tuned by etching the pore walls with various synthesis solvents for different reaction times.

The zeolitic imidazolate framework-8(ZIF-8)is another representative of the zinc-based MOFs possessing high tunable porosity,as well as high thermal and chemical stability.However,the crystal size of conventional ZIF-8 synthesized via various methods(e.g.,solvothermal route,microwave-assisted,sono-chemical,mechano-chemical,chemical vapour deposition)is usually located in the micrometre region[61].In addition,the pore size of conventional ZIF-8 is 0.34 nm,derived from 1.16 nm wide cavities connected by six-membered windows,which is typical of a microporous regime[62,63].Recently,many advanced strategies for reducing crystal size and introducing extended pores in conventional ZIF-8 have been developed.For example,Wee et al.[64]found that nanoscale ZIF-8 crystals can be formed in a solution with 2.2 times more precursors than usual,and crystal sizes of approximately 150 nm,but the as-synthesized nanoscale ZIF-8 mainly possessed micropores from the type I N2adsorption isotherm.Interestingly,the porosity of the nanoscale ZIF-8 crystals was changed when used as a heterogeneous catalyst for selective monoglyceride synthesis through the esterification of oleic acid with glycerol after three runs,in which there appeared mesopores,as confirmed by N2adsorption–desorption isotherms and pore size distributions.The leach of Zn can be attributed to the change in pore size of nanoscale ZIF-8 from micropores to micro-mesopores.These findings point to the synthesis of nanoscale hierarchically porous ZIF-8 via a post-modification process.

Xi et al.[65]reported a versatile strategy to rapidly synthesize a series of zinc-based NHP-MOFs(ZIF-8,ZIF-61 and ZIF-90)at room temperature and pressure,using organic amines as supramolecular templates(organic amine-template).As shown in Fig.8,the organic amine-templates play two roles during the synthesis:(I)a protonation agent to deprotonate ligands,facilitating the nucleation of ZIF crystals,resulting in the formation of small crystals(nanoscale),and(II)a structure directing agent to guide the formation of extended pores(mesopores and macropores).The smallest nanoparticle of the resulting ZIF-8 is approximately 50 nmin size,with pore sizes spanning three ranges(micropores,mesopores,and macropores).The shapes and porosities of the nanoscale hierarchical porous ZIF-8 can be easily tuned by changing the reaction time and the type of organic amine-template,opening up a new avenue for reducing crystal sizes while simultaneously introducing extended pores.However,the disadvantage of the supramolecular template strategy is that the introduced template must be removed through a complex procedure of post-synthesis purification[25,66].

Fig.9.Schematic of the preparation of nanoscale hierarchically porous ZIF-8/PMAC composites.Reprinted with permission from Ref.[68].

Fig.10.Particle size distribution of MOF-gated MS synthesis from different ratios of MS/MOF.Reprinted with permission from Ref.[69].

Abdelhamid et al.[67]reported a versatile and scalable method to rapidly synthesize zinc-based NHP-MOF composites(dye@ZIF-8,MB@ZIF-8,and BSA@ZIF-8)via encapsulating organic dyes(e.g.,rhodamine B(RhB),methylene blue(MB))or proteins(bovine serum albumin,BSA)into ZIF-8 using trimethylamine(TEA).The crystal size and mesopore size could be tuned by changing the Hmim/Zn ratios,or dye concentrations,or TEA.For example,the as-synthesized RhB@ZIF-8 composites with different Hmim/Zn ratios have a broad crystal size distribution from 50 to 200 nm,and the mesopores derived from the addition of TEA were approximately 20 nm.SEM images show that the RhB@ZIF-8 composites with different dye concentrations have a wide particle size distribution from 50 to 200 nm.Furthermore,the mesopores are smaller(<5 nm)at a high RhB concentration(30 μmol RhB)but are larger(10–20 nm)at low RhB concentrations.In addition,this synthesis concept can be used to synthesize a series of nanoscale hierarchically porous Co-based MOF composites,such as RhB@ZIF-67 and MB@ZIF-67.The encapsulation of organic dyes into ZIF-8 increases their lifetimes by a factor of 3–27 compared to the corresponding free dye,allowing them to be used as lifetime sensors or biosensors.

Guan et al.[68]reported a facile in situ growth method for ZIF-8 onto the surface of a mesoporous amino-functionalized ion copolymer(PMAC)to synthesize nanoscale hierarchically porous ZIF-8/PMAC composites.As shown in Fig.9,Zn2+was first coordinated with nitrogen atoms from the amino-alkyl chain of PMAC,and then reacted with a linker(2-methylimizadole)to form cubic ZIF-8 nanocrystals,resulting in the generation of ZIF-8/PMAC composites with ZIF-8 crystals uniformly and tightly loaded on the surface of PMAC.The TEM image of ZIF-8/PMAC composites shows that ZIF-8 with sizes of around 300 nm grew on the surface of the polymer matrix with sizes of around 150 nm.The N2adsorption–desorption isotherms that combine both types I and IV indicate the coexistence of micropores and mesopores.Notably,the mesopores in ZIF-8/PMAC composites are derived from ZIF-8 and PMAC,respectively.The resulting ZIF-8/PMAC composites exhibited improved CO2adsorption performance because the hierarchically porous structures and nanoscale crystals possess a fast rate of CO2adsorption and diffusion.

Wang et al.[69]reported an ultrafast,low-temperature,versatile self-assembly route to synthesize nanoscale hierarchically porous MS@MOF composites(MS:mesoporous silica,MOF:ZIF-8)with MS as a core container and MOF as a gatekeeper.As shown in Fig.10,the DLS shows that the hydrodynamic diameter of MS@MOF composites increases from 100 to 1200 nm with the increase in MOF amount,indicating the formation of nanoscale MS@MOF composites at a low ratio of MS/MOF.The micropores are formed from inherent MOFs and the mesopores are formed by MS with open and stellated pore channels as large as 35 nm.The formation of nanoscale hierarchically porous structure MS@MOF composites is suggested by these findings.SEM images show that as the amount of MOFs increases,the shape of MS@MOF composites gradually changes from isolated~100 nm nanospheres toaggregated~500 nm nano complexes.The as-synthesized MS@MOF composites show synergetic effects,effectively inducing durable tumour suppression in tumour-bearing mice.

Fig.11.Schematic illustration of nanoscale hierarchically porous NH2–MIL-53(Al)synthesized with different solvents.Reprinted with permission from Ref.[70].

2.5.Aluminum-based NHP-MOFs

Recently,some novel synthesis strategies have been developed to reduce the crystal size and increase the pore size of aluminum-based NHP-MOFs and their derivatives to obtain nanoscale hierarchically porous structures.MIL-53(Al)and NH2-MIL-53(Al)are two typical aluminum-based MOFs that have been widely investigated in recent years.Guo et al.[70]described a straightforward method for producing nanoscale hierarchically porous NH2-MIL-53(Al)in a mixed solvent system(DMF–water)without any surfactants or capping agents.The size and shape of NH2-MIL-53(Al)can be readily tuned by varying the composition of the mixed solvents.As shown in Fig.11,with pure DMF as the solvent,the average crystal and particle sizes are 24 nm;when a trace amount of water(water ratio=3.3 vol%)is added to DMF,the average length and width of these small crystals are 201±44 nm and 23 nm,respectively.However,after adding more water,the average crystal size increased from 76±20 nm(water ratio=25 vol%),127±30 nm(water ratio=50 vol%),419±127 nm(water ratio=75 vol%),to 520±120 nm(water ratio=100 vol%).The reason for this is the deprotonation ability of the organic ligand depending on the amount of water in a mixed solvent system,thereby resulting in the generation of different nucleation rates and crystal anisotropy[71].Furthermore,in N2adsorption–desorption isotherms,all NH2-MIL-53(Al)samples synthesized with different water volume ratios in DMF–water mixed solvents exhibit an apparent hysteresis loop,indicating the presence of micropores.In comparison to the addition of surfactants or capping agents,this method is very simple and will not introduce any impurities for NHP-MOF synthesis.

Isaeva et al.[72]reported that a series of flexible aluminum-based NHP-MOFs(MIL-53(Al),NH2-MIL-53(Al),and MixLR(Al3+ions and mixed 2-aminobenzene-1,4-dicarboxylate and benzene-1,4-dicarboxylate ligands,R=1,2,3))were synthesized using microwave-activation under atmospheric pressure.SEM results show that all as-synthesized MIL-53(Al)type materials belong to the nanoscale regime,in which the crystal sizes of MIL-53(Al)and NH2-MIL-53(Al)are 200–300 nm,while MixLR is 20–30 nm.The MW-irradiation technique is responsible for particle size reduction and the formation of nanocrystals with a uniform shape and size distribution.The difference in nanocrystal sizes between as-synthesized MIL-53(Al)type samples with homogeneous linkers and their MixLR counterparts with mixed linkers could be attributed to the different MW-synthesis reaction mechanisms.In addition,N2adsorption-desorption isotherms and pore size distributions indicate that MIL-53(Al)and MixLR possess micropores and mesopores,with a maximum mesopore size at 3.7 nm.The as-synthesized nanoscale hierarchically porous MIL-53(Al)type materials exhibit much higher 2,4-D adsorption rates than a commercial activated carbon matrix.

Some aluminum-based MOFs(e.g.,MIL-53(Al))can be used as a promising host matrix of enzyme immobilization because they possess inherently large mesopores that are enough to accommodate enzymes[3].For example,Gasc′on et al.[73]reported the immobilization of enzymes(e.g.,β-glucosidase or laccase)on MIL-53(Al)and NH2-MIL-53(Al)to synthesize nanoscale hierarchically porous aluminum-based NHP-MOF composites at room temperature using a post-synthesis method or an in-situ strategy,wherein the enzyme was encapsulated into the intercrystalline mesoporosity by a post-synthesis method while the enzyme located in the hollow space between nanocrystals via the in-situ method.SEM images and pore size distributions of aluminum-based MOF composites show mesopores as large as 20 and 30 nm,and powder XRD patterns and SEM images confirm their nano crystallinity.However,the crystalline nanocrystals in particles of several microns are easily agglomerated or aggregated.Moreover,nanoscale hierarchically porous magnesium-based MOF composites(Mg-MOF-74)can also be synthesized via both post-synthesis and in situ strategies.In addition,Sahu et al.[74]reported that lactobionic acid(LA)conjugated NH2-MIL-53(Al)to synthesize LA-embedded NHP-MOF composites with an average particle size 40–50 nm using a single step and green synthetic strategy.The as-synthesized LA-embedded NHP-MOF composites demonstrated excellent targeting of liver tumour cells.However,the biological compatibility of aluminum-based NHP-MOFs and their derivatives for drug delivery is a problem[75].

In addition,the adjustability of MOFs in organic ligands is beneficial in improving the compatibility between MOFs and polymers,such as optimizing the interfacial interaction of different phases[76].For example,Arjmand et al.[77]fabricated aluminum-based NHP-MOF composites based on NH2-MIL-53(Al)as the filler and polyethersulfone(PES)as the polymer matrix.First,the NH2-MIL-53(Al)was amino-silane functionalized by 3-aminopropyltriethoxysilane(APTES)using a post-synthetic modification,resulting in the amine(–NH2)groups located on the surface of MOFs that can reinforce their interaction with the polymer matrix.The PES/functionalized MOF mixture was thenstirred for 12 h before being cast on a flat-bottom Petri dish to produce nanoscale hierarchically porous NH2-MIL-53(Al)/PES composites.Cross-sectional FESEM images show that NH2-MIL-53(Al)nanoparticles with a fairly uniform size distribution of 50 nm(diameter)are uniformly dispersed into the PES matrix with no discernible aggregation or phase segregation,even though the thickness of the PES matrix was in the range of 50–80 μm.Moreover,the apparent hysteresis loop in N2adsorption-desorption isotherms indicates the presence of mesopores.The resulting nanoscale hierarchically porous NH2-MIL-53(Al)/PES composites exhibited an 84% increase in CO2permeability and a 70%increase in CO2/CH4selectivity in comparison to a pure PES membrane.

Fig.13.Schematic of the preparation of nanoscale hierarchically porous UiO-66 using a monocarboxylic acid etching technique with different etching positions.Reprinted with permission from Ref.[86].

2.6.Zirconium-based NHP-MOFs

In the big family of MOFs,zirconium-based MOFs,which show excellent thermal,chemical and mechanical stabilities because of the strong zirconium(IV)-carboxylate bonding,is seen as one of the most promising MOF materials for practical applications[78].Since Cavka et al.[79]first synthesized zirconium-based MOFs in 2008,considerable efforts have been made to design and synthesize various zirconium-based MOFs and their derivates,and to investigate their structures and properties,as well as their various functions and applications[80].

UiO-66 and UiO-66-NH2are the most common zirconium-based MOFs,and have been widely investigated in recent years.The crystal size of conventional UiO-66 and UiO-66-NH2is relatively large yet with relatively small pores[81].Typically,monocarboxylic acids(MAs)(e.g.,benzoic acid,glycine)are used as a modulator to regulate the crystal size,morphology,and porosity of UiO-66 and UiO-66-NH2,in which the introduced MAs not only modulate the rate of nucleation and crystal growth,but also partially replace the original ligand in some cases[82,83].For example,Jiang et al.[84]developed a simple modulator-induced defect-formation route to synthesize nanoscale hierarchically porous UiO-66 using MA as a modulator and an insufficient amount of organic ligand.As shown in Fig.12,on the one hand,thecarboxylic acid forms metal–oxo clusters by bonding to the metal ions;on the other,the alkyl chain pre-occupies the coordination sites,causing structural defects and the formation of the hierarchically porous structure after removal(Fig.12a–f).The SEM image in Fig.12g indicates that the crystal size of as-synthesized UiO-66 is approximately 500 nm,and the TEM image shows worm-like mesopores(Fig.12h),which are also confirmed by N2adsorption-desorption isotherms and pore size distributions.In addition,this strategy is versatile because other nanoscale hierarchically porous zirconium-based MOFs,such as UiO-66-NH2,UiO-66-NO2,UiO-67,and MOF-808 can also be synthesized.Subsequently,Fu et al.[85]modified the modulator-induced defect-formation method to synthesize nanoscale hierarchically porous UiO-66 and used it as the porous stationary phase for high-resolution and high-efficiency electrochromatographic separation.

Fig.14.(a)Schematic of the fabrication of nanoscale hierarchically porous UiO-66 using DA as a modulator.(b)A route to regulate particle size of nanoscale hierarchically porous UiO-66 using TEA as a synergetic modulator.Reprinted with permission from Ref.[87].

Fig.15.(a)Schematic of the fabrication of nanoscale hierarchically porous UiO-66-NH2 via the linker thermolysis method;(b)TEM images of nanoscale hierarchically porous UiO-66-NH2 single crystals.Reprinted with permission from Ref.[88].

Recently,Gu et al.[86]used MAs as etching agents to partially replace the bridging ligands and metal clusters in UiO-66 and UiO-66-NH2,resulting in the formation of two zirconium-based NHP-MOFs.As shown in Fig.13,regardless of the etching position in bridging ligands and/or metal clusters,the departure of partial MOF precursors contributes to the formation of hierarchically porous structures in MOFs with relatively uniform mesopores(3–20 nm,peaking at 9 nm).Furthermore,SEM and TEM images indicate that the crystal size of the as-synthesized UiO-66 can be readily tuned from nanoscale to micrometre by controlling the concentration of propionic acid(PA).Moreover,PA was verified to be a suitable etching agent for etching chemically stable UiO-66 through choosing a series of MAs(e.g.,benzoic acid,formic acid(FA),acetic acid(AA),PA,and butyric acid(BA))with different acidity and carbon chain length.This result has great significance because it is showing the way for the choice of etching agents of MAs.

Subsequently,Gu et al.[87]developed a new strategy for synthesizing nanoscale hierarchically porous UiO-66 with tunable porosity and particle size by simultaneously introducing two functionalized additives(dodecanoic acid(DA),and TEA).DA was used as a mixed ligand to generate structural defect and additional pore space(Fig.14a),and TEA was used as a protonation agent to deprotonate organic ligands,by facilitating nucleation and growth rate to modulate particle size(Fig.14b).The crystal size of the as-synthesized UiO-66 can be readily tuned in the range of 40–270 nm via controlling the amount of TEA,and the average pore size(based on the BJH method)was about 3.4 nm.The resultant UiO-66 could not only act as a vehicle for the intracellular delivery of Cyt c but also regulate their escape from endosome and release into the cytoplasm,because of their perfect blend of the advantages of nanoscale particle size and hierarchically porous structure.

Zhou et al.[88]reported a selective linker thermolysis strategy to synthesize ultrastable nanoscale hierarchically porous UiO-66-NH2,in which the mesopores are derived from the thermolabile linkers that are selectively cleaved from multivariate MOFs(MTV-MOFs)through a decarboxylation process(Fig.15a).Therefore,the prerequisite of this method is the different thermal stability of organic ligands and that these ligands can freely self-assemble with inorganic nodes.Differing from the generation of missing ligands and cluster defects by ligand labilization that takes place in solution,linker thermolysis tends to undergo a cluster aggregation process at relatively low temperatures.The average size of mesopores was 5.5 nm,according to N2adsorption-desorption isotherms and pore size distributions.Nanoparticles had a crystal size of about 500 nm,deducing from TEM images(Fig.15b).Furthermore,the pore sizes of NHP-MOFs could be easily tuned from 0.8 to 15 nm by adjusting the reaction parameters(e.g.,thermolabile linker ratio,temperature,and heat time).Notably,some ultrasmall metal oxide nanoparticles(1–3 nm)were formed from the linker thermolysis and uniformly dispersed throughout the NHP-MOFs.

As for the introduction of additives(e.g.,chelating agent,surfactant)to construct hierarchically porous structures and reduce the size of MOFs:Li et al.[89]reported a green route to synthesize nanoscale hierarchically porous UiO-66 and UiO-66-NH2via introducing a suitable amount of H2O into the conventional synthesis of their counterparts.The higher the H2O/Zr molar ratio,the smaller the particle size of UiO-66 and UiO-66-NH2.For example,when the H2O/Zr molar ratio is greater than 62,UiO-66 forms large agglomerations of small(<20 nm)particles and forms a sponge-like morphology with apparent mesoporous voids,as confirmed by SEM and TEM images.Furthermore,the N2adsorption-desorption isotherms of UiO-66 are type I and type IV,with pore sizes ranging from 8 to 17 nm.The mechanism can be explained in that the introduction of H2O decreased HCl concentration in the synthesis system,resulting in a weaker competition of Cl-and ligand(BDC2-),thereby forming structure defects[90].Moreover,the as-synthesized nanoscale hierarchically porous UiO-66/UiO-66-NH2showed enhanced catalytic activity in esterification/Knoevenagel reaction and excellent adsorption capacity for Rhodamine B.

2.7.Chromium-based NHP-MOFs

MIL-101(Cr),which inherently possesses a nanoscale hierarchically porous structure,is a representative chromium-based MOF,in which the crystal size is about 500 nm and the mesopore cages have free diameters of 2.9 and 3.4 nm accessible through two micropore windows of 1.2 and 1.6 nm,respectively[91].Recently,some advanced methods for further reducing crystal size or increasing pore size of conventional MIL-101(Cr)have been developed.These are thought to be critical for improved performance in MOF practical applications[92,93].For example,Sun et al.[94]used a grind method to rapidly synthesize nanoscale hierarchically porous MIL-101(Cr)(denoted as MIL-101(Cr)-1.5-4)without theuse of additives(e.g.,solvent,hydrofluoric acid).The crystal particle of the as-synthesized MIL-101(Cr)-1.5-4 is around 40–200 nm,which is smaller than those of conventional MIL-101(Cr)(300–500 nm)synthesized with the solvothermal method.Compared with favourable crystallization in solvothermal conditions,the rough grind atmosphere enables the formation of crystal defects with irregular granular shape in MIL-101(Cr)-1.5-4.However,the pore size of MIL-101(Cr)-1.5-4 is similar to that of conventional MIL-101(Cr),with mesopore diameters centred at 2.9 and 3.4 nm.Because of its smaller crystal size,MIL-101(Cr)-1.5-4 showed a superior catalytic activity in the oxidation of cyclohexene to that of conventional MIL-101(Cr).

Fig.16.Schematic of single-,double-,and triple-shelled hollow MIL-101 MIL-101(Cr)synthesis.Reprinted with permission from Ref.[95].

Fig.17.Schematic of yolk-shell MIL-101(Cr)@mSiO2 nanoreactors synthesis.Reprinted with permission from Ref.[96].

Huo et al.[95]developed a facile strategy to synthesize single-crystalline multi-shelled hollow MIL-101(Cr)with nanoscale crystal size and hierarchically porous structure via step-by-step crystal growth and a subsequent etching processes.As shown in Fig.16,after forming inhomogeneous MIL-101(Cr)crystals via a hydrothermal reaction,the as-synthesized MIL-101(Cr)crystals were immersed in acetic acid aqueous solution,where the less stable section of inner crystallites were preferentially etched,resulting in the formation of a hollow motif.Furthermore,the use of inhomogeneous MOF crystals as templates to repeat the growth-etching process for a second or third time has enabled the successful synthesis of NHP-MOFs with multi-shelled hollow structures.Notably,the hierarchically porous structure in MOF crystals is derived from a multi-shelled hollow structure,and the crystal size of multi-shelled hollow MIL-101(Cr)is determined by the number of hollow layers.The cavity size and shell thickness of MIL-101(Cr)can be precisely tuned by controlling the etching time and the reactant concentration for the synthesis of each layer.The resulting multi-shelled hollow MIL-101(Cr)has significantly higher catalytic activity in styrene oxidation than its counterpart.However,the prerequisite for this strategy is a difference in instability in the interior of the MOF crystals,one which results in selective etching.

In comparison to the previous acid etching method,the etching of MOF surface applied water is a green,environmentally friendly and costeffective method.For example,Yu et al.[96]reported a green route to synthesize nanoscale hierarchically porous MIL-101(Cr)@mSiO2composite with a yolk-shell structure via a water-etching strategy.As shown in Fig.17,an mSiO2shell was first applied to the surface of as-synthesized MIL-101(Cr),followed by the removal of the introduced hexadecyl trimethyl ammonium bromide(CTAB)soft template in the product via a simple extraction process.Finally,the product was etched with hot water to produce nanoscale hierarchically porous MIL-101(Cr)@mSiO2with a yolk-shell structure.TEM and SEM images showed that the crystal size of MIL-101(Cr)@mSiO2is 300 nm,and the pore size distribution curve showed that MIL-101(Cr)@mSiO2has larger mesopores with a broader pore size ranging from 4.0 to 13.8 nm.In practical application,the mesoporous nanoshells in MIL-101(Cr)@mSiO2provide accessible pathways for large guest molecule mass transport,while the yolk-shell structure protects the catalytic active MIL-101(Cr)cores and slows the decomposition of MOF crystals.Therefore,the synergistic effects between MIL-101(Cr)core and SiO2yolk shells can enhance their catalytic activity and stability.Notably,encapsulating MOFs in high-stability shells of inorganic SiO2improves the chemical and physical stability of pure MOFs,expanding the range of MOF applications,particularly in harsh application environments such as high temperature and pressure,alkali-or acid reaction systems.

Fig.18.(a)Schematic of nanoscale hierarchically porous FJI-C10 synthesis,and the pore size distribution(b)and SEM of FJI-C10.Reprinted with permission from Ref.[97].

Cao et al.[97]reported the synthesis of nanoscale hierarchically porous MIL-101(Cr)derivate,termed FJI-C10,using a mixed-ligand method.As shown in Fig.18a,2-(3-ethyl-imidazole-1-yl)-terephthalic acid[(Etim-H2BDC)+(Br-)]was selected as a mixed ligand,resulting in the formation of mesopores in the FJI-C10 framework.The pore size distribution of FJI-C10 revealed open cages with internal free diameters of~2.1 and 3.1 nm(Fig.18b),and SEM and TEM images showed that the crystal size was between 100 and 400 nm(Fig.18c).Furthermore,the introduced mixed ligand creates Lewis acidic Cr3+sites and free halogen ions on the robust mesoporous framework,resulting in the as-synthesized FJI-C10 exhibiting higher catalytic efficiency than other typical MOF catalysts,such as HKUST-1 and ZIF-8.Notably,the introduction of functionalized mixed ligand in MOFs synthesis not only generates mesopores but also brings new properties in practical application[98,99].

In addition,some metal nanoparticles(e.g.,Ni,Pd,and Sn)were loaded in MIL-101(Cr)to form MIL-101(Cr)composites.Because of the introduction of metal nanoparticles it hardly changes the pristine crystal size and hierarchically porous structure of MIL-101(Cr).Thus the obtained MIL-101(Cr)composites generally belong to the nanoscale hierarchically porous regime[100].The as-synthesized nanoscale hierarchically porous MIL-101(Cr)composites not only combine their respective merits but also exhibit synergistic functionalities[101,102].For example,Terasaki et al.[103]reported the synthesis of a series of nanoscale hierarchically porous MIL-101(Cr)composites(e.g.,TiO2-in--MIL-101-Cr,TiO2-in-MIL-101-Cr-NH2,and TiO2-in-MIL-101-Cr-NO2),growing TiO2in conventional MOF mesopores,and the internal growth of TiO2resulted in the formation of molecular compartments within MOF crystals.According to the Raman spectroscopy and pair distribution function(PDF)results,the introduced TiO2units exist in molecular compartments primarily in the form of anatase,which exhibits excellent photocatalytic performance[104,105].The crystal size of these MIL-101(Cr)composites barely changes in comparison to pure MIL-101(Cr)because of TiO2growth inside in mesopores of MOFs,whereas some mesopores were filled with a sequence of TiO2units.

3.Conclusions and outlook

Compared with conventional MOFs,including microporous MOFs,hierarchically porous MOFs,bulk MOFs,and nanoscale MOFs,nanoscale hierarchically porous metal–organic frameworks(NHP-MOFs)combine the merits of both nanoscale and porosity and exhibit exceptional properties.For example,in NHP-MOFs,the nanoscale size is advantageous because it shortens the diffusion path for guest molecules from the surface to the crystal interior and provides more accessible active sites for surface reactions,whereas a hierarchically porous structure is advantageous because it facilitates diffusion and accessibility of guest molecules.Based on these advantages,various advanced strategies for synthesizing NHP-MOFs to meet the needs of various fields have been developed.We have summarized the main synthetic strategies for NHP-MOFs based on different metal ions(e.g.,Cu,Fe,Co,Zn,Al,Zr,and Cr)in this review,including the template method,composite technology,post-synthetic modification,in situ growth method,and grind method.These methods aim to reduce the crystal size of conventional MOFs to the nanoscale while simultaneously extending the micropores to mesopores and/or macropores,resulting in the successful synthesis of NHP-MOFs.

To date,although NHP-MOF synthesis has made encouraging progress,some essential aspects should be considered or improved to realize large-scale production and commercial applicability.(i)Although many NHP-MOFs have multimodal hierarchically porous structures with micropores,mesopores and/or macropores,the size distribution of the mesopores and macropores is usually random.(ii)Most studies focus on tuning the crystal size and porosity of NHP-MOFs,with less attention paid to their stability(mainly solvent,chemical,thermal stability),particularly in harsh environments(e.g.,high temperature and pressure,acidic or alkali solution).(iii)Current experimental steps or physical techniques in these methods are labour and resource intensive,rarely considering the prerequisites of the commercial process,such as low-cost raw materials,facile synthesis conditions,and simple production process.(iv)Although these synthesis strategies have been demonstrated,the mechanism remains unclear,resulting in the theoretical and technical design of NHP-MOFs still being challenging,prompting a long and difficult exploration process.(v)Although computational approaches can provide a more in-depth understanding of the synthetic process and the structure-performance relationship,there have been few reports on the use of computational approaches to study NHP-MOFs.(vi)Currently,NHP-MOF synthesis is still at the laboratory level with gram level rather than continuous manufacturing with kilograms or even tonnes.When considering large-scale production,the coincident structural properties of NHP-MOFs must not be overlooked.(vii)When used in industrial applications,most of the reported NHP-MOFs are polydisperse microcrystalline powders rather than being monolithic,resulting in dustiness,abrasion and clogging,as well as decreased pressure.(viii)Currently,NHP-MOF potential applications are relatively few;more effort needs to be devoted to exploring more innovative applications.To summarize,there are still quite a lot of challenges before realizing large-scale production and commercial applications,and more effort has to be devoted to optimize their production engineering or develop novel synthesis methods toward more simple and efficient processes.With persistent endeavour,it is believed that NHP-MOFs should present a promising future.

Declaration of competing interest

None.

Acknowledgements

We gratefully acknowledge the financial support from the National Natural Science Foundation of China(22008032,22108034,and 22102026),the Guangdong Basic and Applied Basic Research Foundation(2019A1515110706),the Guangdong Provincial Key Lab of Green Chemical Product Technology(GC202111),the Medical Science and Technology Research Foundation of Guangdong Province(A2021189),and the Shandong Provincial Natural Science Foundation(ZR2018ZC1458).