Research will be limited to:
- Material: MOF-5
- Method: Solvothermal Synthesis
- Reactants: Zinc Nitrate, Terephthalic Acid, DMF
- Process: Solvent Exchange Activation

Strategy: The objective is to retrieve the precise experimental protocol for MOF-5 synthesis using the specified precursors (Zinc Nitrate, Terephthalic Acid, DMF) via solvothermal methods, with a specific focus on the activation parameters and solvent exchange procedures (typically using chloroform or dichloromethane) to ensure porosity. I will search for the foundational and optimized protocols that detail temperature, duration, and the specific solvent exchange steps required to prevent framework collapse.
Queries:
- MOF-5 solvothermal synthesis zinc nitrate terephthalic acid DMF protocol
- MOF-5 activation solvent exchange chloroform dichloromethane procedure
- solvothermal synthesis MOF-5 temperature time DMF zinc nitrate hexahydrate
- MOF-5 pore activation solvent exchange drying conditions protocol
- optimization of MOF-5 synthesis solvothermal DMF solvent exchange activation

Executing 5 concurrent searches:
- MOF-5 solvothermal synthesis zinc nitrate terephthalic acid DMF protocol
- MOF-5 activation solvent exchange chloroform dichloromethane procedure
- solvothermal synthesis MOF-5 temperature time DMF zinc nitrate hexahydrate
- MOF-5 pore activation solvent exchange drying conditions protocol
- optimization of MOF-5 synthesis solvothermal DMF solvent exchange activation

Found 5 papers. Key excerpts:

Scalable continuous solvothermal synthesis of metal organic framework (MOF-5) crystals — Colin McKinstry et al., 2016

Metal–organic framework (MOF) materials [1] are of considerable interest due to the unique properties granted by the nature of their supramolecular construction [2] , [3] . This method of material design allows MOFs to be potentially tailored in aspects such as pore size and bonding strength by careful choice of the metal ion centre [4] and ligand group [5] used. Ligands with side-chains can be used to allow further functionality to the material, allowing for the possibility of a truly tunable system at the molecular level [6] . The ability of three-dimensional MOFs to form scaffold-like structures reduces the dead space within a bulk volume to almost zero, providing considerable benefits to gas processing using MOFs. Their tailored syntheses has allowed several MOFs to have surface areas larger than that deemed possible in carbon structures or zeolites [6] . As such, MOFs have great potential in gas storage and separation processes, catalysis and use in medical devices.
However, as most procedures for MOF synthesis are small-scale batch processes, only rare studies report production on the order of kg scale [7] . Many MOF syntheses require expensive ligands or the use of costly and non-reusable solvents. MOF syntheses are reported in the literature to be via wide variety of batch routes, including solvothermal [8] , ultrasonic enhanced [9] , microwave heated [10] , diffusion or direct addition of amines [11] and growth on substrates [12] . Solvothermal synthesis is the most commonly applied synthetic route, allowing the system to be operated without the need for specialist equipment and the relatively fast growth of crystals with high levels of crystallinity, phase purity and surface areas [13] . While synthetic techniques, including mechanochemical synthesis, can reduce solvent usage significantly when producing MOFs with high yields, such routes incur heat transfer issues and high mechanical energy requirements on scale up that may limit applications [14] . Although this route has shown promise with scalability for some MOFs, it has been highlighted that this route is dependent on the ability of the MOF to withstand the mechanical and thermal strains of mechanochemical synthesis [15] and hence it is not suitable for all MOFs.
The high synthetic costs of MOFs have impeded the development of viable industrial uses; for MOFs to be economically viable, a reduction in the unit cost via scale

-up, and switching from batch to continuous processing, is required, which has been confirmed by our preliminary process economics analysis [16] . Continuous methods offer several benefits compared to more traditional batch systems that are used to produce MOFs at the current time, such as higher output per unit time and, theoretically, zero downtime. Furthermore, when a reactor reaches steady state, the product output from the system is consistent, and eliminates variability that would be seen between batches. The capital cost and design complexity of continuous processing is increased compared to batch systems but the benefits in output can outweigh this issue, allowing greater economic viability [17] .
Microfluidic reactors have been used, and with promising results for many materials, including HKUST-1, MOF-5 and MIL-53, three prototypical MOFs. Microfluidic reactions rely upon formation of nanoliter scale droplets which results in efficient heat and mass transfer, while also providing a very high surface area to volume ratio [18] . MOF-5 has been synthesised using a continuous microfluidic reactor, resulting in the formation of MOF-5 in 3 min at 120 °C, a significant reduction in reaction duration at this temperature, and BET surface area of 3185 m 2 g −1 . IRMOF-3, with different composition but the same topology as MOF-5 was also synthesised in similar times. UiO-66 was shown to be synthesised in 15 min at 140 °C using the same approach [18] . However, microfluidic syntheses are not necessarily scalable since transport properties scale non-linearly with production scales [19] , [20] . In terms of scalability, microfluidic systems rely upon the very high surface area to volume ratios and the heat transfer and mass transfer of single droplets of reaction solution, usually under 200 μm in diameter, in oil. While control over these droplets can increase throughput, the current upper limit appears to be in the order of hundreds of ml h −1 [21] and so scalability may be an issue despite the benefits of using microfluidics.
Recent advances have shown it is possible to produce UiO-66-NH 2 in a scalable reaction system [22] . HKUST-1, previously produced using the microfluidic approach has also shown promise at larger scales of continuous processing. Gimeno-Fabra et

al. [23] showed the ability to form high quality HKUST-1 using a counter-current flow reactor operating at 300 °C and 250 bar, bringing the required synthesis time for HKUST-1 from hours by conventional synthesis to 1 s while maintaining a high surface area. Kim et al. [18] reported continuous production of HKUST-1, showing the capability of producing high yields of high quality crystals in reaction times as short as 5 min with considerably less harsh operating conditions than Gimeno-Fabra et al., though still operating at 100 bar. Rubio-Martinez et al. [24] reported the ability to make HKUST-1, UiO-66 and NOTT-400 in a continuous process and demonstrated the ability to scale the reaction volume of HKUST-1 from 10 ml to 108 ml while maintaining the high surface area of the MOF, with higher reported surface area than Kim et al. Further, this system operates at pressures relatively close to atmospheric conditions, reducing the intrinsic risk of the process. Bayliss et al. synthesised MIL-53 in a potentially scalable system, showing a reduction in synthetic duration from the order of days to minutes, with surface area consistent with prior literature though significantly, pressure of 100 bar was used for this system [25] . Increasing the temperature and pressure for MOF synthesis has been shown to provide thermodynamic conditions that result in the formation of the framework in considerably shorter times than previously reported in the literature [26] , however operating at elevated temperatures and pressures is likely to increase the overall cost of the process significantly.
In this study, we focus on production of MOF-5, which has the composition Zn 4 O(BDC) 3 (BDC = benzene dicarboxylate anion) [27] . MOF-5 has been a material of great interest in the scientific literature due to the high surface area, since the structure was first published in 1999. Although they have been recently surpassed in some key criteria by other MOFs, the zinc-carboxylate MOFs represent a large family of isoreticular structures which are anticipated to have useful applications in the future. Further, despite continuous syntheses reported at small scales, there are no reports on the large-scale production of MOF-5. Therefore, we selected MOF-5 as a model system, and developed a continuous process for its synthesis, which could facilitate the development of

Atomistic structures and dynamics of prenucleation clusters in MOF-2 and MOF-5 syntheses. — Junfei Xing et al., 2019

Introduction Metal-organic frameworks (MOFs) are porous minerals that consist of nodes comprising metal ions connected by organic linkers 1 , 2 . Their diversity in lattice structure, elemental composition and organic linkers offers tremendous opportunities in materials applications 3 , 4 . Easy access to diverse structures is an asset of MOF science and technology, but their synthesis often shows hints of mechanistic complexity. As a classic example, MOF-2 having square lattice and MOF-5 having cubic lattice (Fig.  1a ) 5 differ only in the conditions of the reaction between zinc nitrate and benzene dicarboxylic acid (H 2 BDC) in dimethylformamide (DMF): heating at 95 °C for several hours produces MOF-2 (Zn:BDC = 1:1, isolated in its DMF solvated form) 6 , and the mixture becomes acidic (Zn(NO 3 ) 2  + 2•RCOOH = Zn(RCOO) 2  + 2•HNO 3 ). Heating at 120 °C produces between 0 and 4 h non-porous precipitates of unknown structure (Zn:BDC = 1: 1, called herein as X ) 7 , which gradually changes in situ to MOF-5 nanocrystallites as the solution changes from acidic to basic 8 because of thermal decomposition of DMF that generates a formal water dianion (O 2− or Zn + −O − ) 9 . For a few tens of hours after formation, the nanocrystallites undergo Ostwald ripening to produce MOF-5 cubic polycrystals (Zn:BDC = 4:3) 10 . Thus, the system conforms the kinetics and thermodynamics of the reaction intermediates that serve as prenucleation clusters (PNCs) of crystallisation controlled by interface and bulk free energetics (Fig.  1b ) 11 . Although the MOF-2/-5 bifurcation suggests structural difference among the PNCs leading either MOF-2 or MOF-5 (Fig.  1c ) 12 , 13 , little has been known for PNCs in solution at molecular level 14 . Earlier in situ studies by static light scattering

15 , extended X-ray absorption fine structure 16 , and liquid cell transmission electron microscopy (TEM) 17 revealed small crystals but not PNCs 12 , 13 . PNCs were identified only by mass spectrometry 18 and by computer simulation 19 . In this context, we focused on the MOF-2 and -5 formation 20 through in situ capturing of PNCs and atomistic structural analysis by single-molecule atomic-resolution real-time electron microscopy (SMART-EM) 21 , 22 . Fig. 1 Formation mechanism of MOF-2 and MOF-5 crystals from Zn 2+ and BDC. a Temperature-dependent bifurcation to MOF-2 and MOF-5 formed from zinc nitrate hexahydrate and H 2 BDC. H 2 IBDC yields isostructural I-MOF-5. See Supplementary Fig.  18 for crystal structure. b Overall pathway of MOF formation that consists of two stages, and capturing of PNCs on BDC-CNHs. c Schematic illustration of the reaction paths from LO PNCs to cube PNCs, and to MOF-2 and -5 crystals. d Structures of nodes consisting of Zn 2+ and BDC In Fig.  1d , we summarise the correlation between the node structures based on reported crystal structures. The mononuclear structure of a digonal node A is ubiquitous among zinc carboxylates 23 and forms linear polymers of Zn-BDC as found commonly in the MOF-2 and -5 synthesis. The dinuclear complex B is simply a dimer of A responsible for the formation of square PNCs, and represents a tetragonal node in MOF-2. The structural relationship between the mononuclear node A and a tetranuclear node D parallels the one between zinc acetate and basic zinc acetate (Zn 4 O(CH 3 COO) 6 ), the latter converted readily to the former upon acidification 20 . The trinuclear node C is an intermediate to D formed by replacement of one RCOO – group on B by Zn + −O −
24 . Thus, the formation of D (MOF-5 node) from C requires the addition of one zinc cation and three molecules of BDC, with a

considerable entropy loss 25 , 26 . This chemical diagram suggests that the linear and square (lower order, LO) PNCs made only of Zn and BDC should form readily under mild conditions, while the cube and cube-like (higher order, HO) clusters requiring nodes C and D should increase in number as DMF decompose upon prolonged heating at 120 °C. We verified this hypothesis experimentally by SMART-EM studies of the clusters isolated from the reaction mixture as described below. Here, we report that the MOF-2 synthesis produces square-shaped clusters, while the MOF-5 synthesis produces cube and cube-like clusters as structurally the most complex PNCs (Fig.  1c ). Commonly found in both cases were linear clusters of considerable structural flexibility - zinc carboxylate oligomers (Fig.  1c, d (A)). In the synthesis of iodinated MOF-5 (I-MOF-5) from 2-iodoterephthalic acid (H 2 IBDC), we established the structure of a slowly rotating 1.3-nm-sized cube cluster by determining the spatial locations of all 12 iodine atoms in sequential 2-D video images with approximately 1 Å precision. The SMART-EM technique recently revealed the feasibility of single-molecule level kinetics 27 – 30 , and now allows us to investigate atomistic structures of minute intermediates of chemical reactions. Results Capturing PNCs of MOF-2 and MOF-5 on BDC-CNH For this study, we designed a ‘fishhook’ for the in situ ‘fishing’ of PNCs, and connected BDC molecules as such a fishhook via an amide linkage onto carbon nanohorn aggregates (BDC-CNH; Fig.  2a, b ). Being a part structure of the covalent network of MOF crystals, the BDC group on CNH serves as a chemically powerful “fishhook” for capturing PNCs in solution so that we can study their structure one by one by EM. Thus, we heated a mixture of H 2 BDC (or H 2 IBDC), Zn(NO 3 ) 2 •6H 2 O (2 equiv), and BDC-CNH (1 × 10 −2 −10 −3 molar equiv –NH

Thermodynamics of solvent interaction with the metal–organic framework MOF-5 — Zamirbek Akimbekov et al., 2016

Introduction

The synthesis of metal organic frameworks (MOFs) has attracted immense attention during the last two decades due to the ability to obtain a large variety of scientifically interesting highly porous structures that could have applications for gas storage, separations, catalysis, and sensors, based on the pore size and shape as well as the host -guest interactions involved. Although a myriad of MOFs has been reported, numerous predicted structures are yet to be prepared experimentally. To circumvent kinetic and/or thermodynamic limitations of direct techniques, innovative synthetic routes such as solvent assisted linker exchange (SALE) and transmetallation are indispensable. By using these techniques, previously unobtainable MOFs (e.g. metastable MOF-5 analogues, Cd-ZIFs) have been prepared. 8,10 One of the most crucial parameters in all these strategies, including hydro/solvothermal, SALE, and transmetallation, is solvent. 8 3 (MOF-5) bind solvent molecules, thereby converting MOF-5, previously believed to be a robust structure, into a dynamic system that incorporates intricate host -guest interactions. 10 Comprehension of dynamic solvent -MOF-5 binding allowed synthesis of previously the unattainable metastable ZnCo 3 O(C 8 H 4 O 4 ) 3 structure through transmetallation. 10 However, previous thermochemical investigations on MOF-5 with excess DEF loading suggest very weak solvent -MOF interactions (-5.2 +- 1.6 kJ(mol of ZnDEF) -1 ) and that solvent acts largely as space filler and hence there is no genuine bond between DEF and MOF-5. 11 Nevertheless, in that report, due to the excess loading of guest molecules, the measured energetic values might have included not only DEF -MOF interactions but also solvent -solvent interactions in the interface and void space of the MOF. Therefore, in the present study, to determine the energetics of solvent -Zn 4 O binding, MOF-5 samples with low guest contents (MOF-5 * 1.0DMF and MOF-5 * 0.60DEF, see Figure 2) were prepared.
Some thermodynamic terms used in this work are defined below. The solution enthalpy ([?]H s ) represents the energy released or absorbed when the sample pellet dissolves

in the solvent (5 M NaOH, at 25 o C). 11,12 By using a thermodynamic cycle (Tables 1 and 2) based on Hess's law and state function properties of enthalpy, the [?]H s of each step was used to determine the enthalpy of reaction ([?]H rxn ),namely the enthalpy of formation ([?]H f ) of MOF from ZnO, organic linker and solvent. Additionally, the interaction enthalpy ([?]H int ), which represents the binding strength of molecules (DMF/DEF) with MOF-5, was derived by taking differences of [?]H f of activated (solvent-free) MOF-5 and DMF/DEF occluded MOF-5.

Experimental Methods

a) Synthesis

Zinc nitrate hexahydrate (Zn(NO 3 ) 2 *6(H 2 O)) (0.446 g, 2.355 mmol) and 1,4-benzenedicarboxylic acid (0.083 g, 0.499 mmol) were dissolved in 49 mL of anhydrous N,N-dimethylformamide (DMF) and 1 mL of deionized water in a 100 mL jar with a Teflon cap. These contents were added to an oven preheated to 100 oC and kept there for 7 h. After cooled to room temperature, the crystals were collected by gravity filtration under an inert atmosphere of N 2 in a bench top glovebag. They were transferred under N 2 to a N 2 -filled glovebox and washed six times with fresh DMF, waiting 8 h between each wash, and then with di-chloromethane (CH 2 Cl 2 ) in a similar manner. The solid was collected by gravity filtration and heated to 180 oC for 12 h under 10 -5 torr pressure. 25 mg of fully evacuated MOF-5 was suspended in 5 mL of DMF/DEF and left for at least 12 h. The DMF/DEF was replaced by 20 mL of CH 2 Cl 2 , left for 8 h, then solvent was replaced two more times. The resulting crystals were placed under reduced pressure at room temperature for several hours with no additional heating.

b) Thermogravimetric analysis (TGA)

All TGA experiments were performed

on a Netzsch Liquid DMF was injected through a teflon tube that extended through the silica connection tube to approximately 2 cm above the solvent surface. The mass of injected DMF was determined by weighing the syringe assembly before and after DMF injection. The dry masses of the syringe and Teflon tube were known, allowing the amount of DMF injected into the calorimetric cell to be calculated. All the weight measurements involving DMF were done on a Mettler microbalance with an accuracy of 10 ug. Mechanical stirring at approximately 1/2 Hz was applied to all experiments. After each experiment the cell was removed, reassembled with fresh solvent, and reequlibrated in the calorimeter for at least 6 hours before the next measurement. For each sample, we performed 4 -6 measurements and took their average as the final value. The uncertainty reported in each enthalpy represents the 95 % confidence interval. The calorimeter was calibrated by dissolving 15 mg pellets of NIST standard reference material KCl in 25 g of water, which corresponds to a reference concentration of 0.008 mol kg -1 at 25 degC. The calibration factor was calculated using the known solution enthalpy for the reference concentration of 0.008 mol kg -1 and enthalpy of dilution measurements. The total heat effect due to sample dissolution was obtained by integrating the calorimetric signal with a linear baseline, which was then converted to joules, using the calibration factor obtained using KCl. This methodology has been described previously. 11,12

Results and Discussion

To confirm single phase and composition, MOF-5 samples were analyzed by powder Xray diffraction and TGA, see Figure 3. Both samples have X-ray diffraction patterns similar to that of MOF-5 reported in the literature. 13 energetically metastable with respect to their dense phase assemblages. Incorporation of solvent diminishes but does not eliminate the energetic metastability.
The enthalpies of interaction of DMF and DEF with the Zn 4 O node in MOF-5 are -82.78 +- 4.84 kJ(mol DMF) -1 and -89.28 +- 3.05 kJ(mol DEF) -1 . Note that in the thermodynamic cycles and calculated enthalpies of interaction, the standard state

Dynamic DMF Binding in MOF-5 Enables the Formation of Metastable Cobalt-Substituted MOF-5 Analogues. — Carl K Brozek et al., 2015

INTRODUCTION

Dynamic motion is pervasive and functionally critical in natural and synthetic chemical systems. Enzymes, such as methane monooxygenase, bend and contort interior channels to ensure that substrates, like methane, arrive at the active site just on time. 1 Heterogeneous catalysts are no less dynamic: the oxidation of H 2 on Pt(111) requires that the surface Pt atoms spontaneously shuffle into a new morphology. 2 Even in energy storage systems such as Al-ion batteries, recently reported ultrafast charging likely implies unusual transport of [AlCl 4 ] - anions through dynamic, flexible three-dimensional pores. 3 In these and many other examples, crystal structures are not adequate descriptors of the dynamic motions occurring in a given molecule or material. However, whereas probing the dynamic motion in soft materials such as proteins and enzymes is well established, 4 an appreciation for the dynamism of harder materials, and its critical role in the function of these materials, has been gaining momentum only more recently.
One class of materials that has seen tremendous growth in this space is MOFs. Although snapshots of dynamic, mechanical motion in these materials can sometimes be gleaned from crystallography, as is the case with "breathing" frameworks, 5-7 many materials in this class exhibit properties that are inconsistent with the static view typically conveyed by their crystal structures. For instance, guest molecules that are significantly larger than the pore openings, such as enzymes, can sometimes be adsorbed into the pores. 8,9 Furthermore, the organic ligands and secondary building units (SBUs) can be exchanged in numerous MOFs by simply soaking them in solutions of the inserting components. 10,11 In another body of literature, catalysis occurs at SBUs where metal centers have no available binding sites, yet the catalytic transformation involves inner-sphere reactivity and must proceed through bond formation between a substrate and a metal center. 12-16 Defects aside, 17 for these and other phenomena to occur, the metalligand bonds in MOFs likely dissociate and, in the case of ligand or metal exchange or SBU-based catalysis, new metalligand bonds are formed.
Herein, we report experimental evidence that the Zn 4 O SBUs in MOF-5, an iconic example in this class of materials, interact dynamically with solvent molecules even in native MOF-5, in liquid DMF. In

the presence of coordinating solvents, this material contains not just tetrahedral Zn ions but also octahedral metals. We also report that the surprisingly dynamic coordination environment of Zn ions in MOF-5 allows the synthesis of metastable MOF-5 analogues that are not accessible by typical solvothermal routes. Due to its ubiquity in the field, demonstrating that MOF-5 is a dynamic structure, with Zn ions that can shuffle fast between four-and six-coordinate geometries, suggests that the SBUs in other MOFs may also be less rigid than previously believed.

RESULTS AND DISCUSSION

We first suspected that Zn 2+ ions of MOF-5 interact with solvent molecules during a routine characterization of an as-synthesized sample. We followed a previously reported procedure that was optimized to remove excess solvent molecules from the pores and to maximize surface area. 18 Zn(NO 3 ) 2 *6H 2 O and 1,4-benzenedicarboxylate were dissolved in DMF containing 2% deionized water and heated for 7 h at 100 degC. The crystals were collected and washed with fresh DMF every 8 h for 2 days and then soaked in CH 2 Cl 2 with similar repetitions. Surprisingly, although this treatment was reported to remove excess DMF, a Fourier transform infrared spectrum (FT-IR) of a sample that had been fully washed with CH 2 Cl 2 , but not evacuated, showed a resonance at 1665 cm -1 corresponding to the CO stretch of DMF (inset of Figure 1). Furthermore, a TGA profile of the same sample exhibited a well-defined mass loss around 50 degC (shown in Figure 1). 19,20 Because of its unambiguous and reproducible "step-like" change, we were able to quantify this mass loss and discovered that it corresponds to exactly two molecules of DMF per formula unit, Zn 4 O(BDC) 3 . The mass loss was further identified as DMF by measuring a TGA of CH 2 Cl 2 -soaked MOF-5 in-line with a mass spectrometer (MS). This confirmed that the weight loss step between 50 and 150 degC corresponds to the release of DMF (Figure 1). Together, the FT-IR and TGA-MS data showed that unactivated or as-synthesized MO

F5 contained up to two bound DMF molecules per formula unit.
Surmising that the most likely binding sites for DMF are Zn 2+ ions in the Zn 4 O SBUs, we sought structural evidence for this surprising solvent-SBU interaction. Although X-ray diffraction would be an obvious choice for such studies, solvated crystals of MOF-5 diffracted very poorly. The diffraction quality of MOF-5 crystals improved only upon heating, suggesting again that as-synthesized MOF-5 suffers from long-range structural disorder or otherwise fast dynamic processes that can only be eliminated by evacuating the solvent molecules. 21 In the absence of X-ray diffraction data, we sought to obtain structural information on DMF interacting with the Zn 4 O SBUs from solid-state 67 Zn nuclear magnetic resonance spectroscopy ( 67 Zn NMR). 22-24 A previous 67 Zn NMR study of MOF-5 yielded high quality spectra, but focused only on the fully evacuated samples or samples that were first fully evacuated and then subsequently soaked in noncoordinating solvents such as chloroform. 25 Our 67 Zn NMR examination of a sample of DMF-soaked MOF-5 with natural abundance of 67 Zn (4.1%) for 20 h at 21.1 T and under magic-angle spinning (MAS) conditions revealed no discernible NMR signal ( Figure 2A (bottom)). However, a fully evacuated sample produced a well-resolved signal under otherwise identical conditions (Figure 2A (top) and Figure S3). This comparison clearly indicated that the presence of DMF affected the 67 Zn NMR parameters in MOF-5, but further experiments and a significantly improved signal-to-noise ratio were needed to identify the exact nature of the interaction of DMF with solvated MOF-5.
To increase the sensitivity of the 67 Zn NMR signal, we synthesized MOF-5 from 97%-enriched 67 Zn metal. A new 67 Zn NMR spectra of MOF-5 taken under magic-angle spinning conditions at 21.1 T: fully evacuated (top) and when solvated with DMF using enriched (middle) and natural abundant (bottom) zinc. Asterisks denote spinning side bands. The spectral inset (blue) illustrates the secondary site present

Identifying pathways to metal-organic framework collapse during solvent activation with molecular simulations. — Joseph R H Manning et al., 2023

Metal–organic frameworks (MOFs) are a class of porous crystalline materials which have shown potential for a range of applications. 1 Their structure, consisting of organic linkers connecting clusters of metal atoms, creates a phase-space with unparalleled diversity – over 100 000 MOFs have been experimentally synthesized to date, 2–5 and several million more hypothetical structures have been identified. 6–10 MOFs are the subject of intense research due to their record-breaking levels of porosity, 11–15 modular construction enabling fine-tuning of metal 16–18 and linker 19–22 chemistry, and the resultant diversity in terms of materials properties. 2,23–27 Accordingly, there have been many studies focusing on the applicability of MOFs to industrially important small molecule separation 1,28–30 and storage 31–34 applications.
A key challenge in synthesizing MOF materials lies in their ‘activation’ after synthesis, a step which removes solvent adsorbed within the MOF's pores during the synthesis procedure. 35–37 Activation is essential to open up the surface area of MOF materials, a requirement for the vast majority of their applications. However, improper activation can easily lead to the pore structure becoming inaccessible, rendering the resultant materials useless. 38 Detailed experimental studies have identified a range of plausible causes for poor activation including incomplete guest removal, surface blocking of the accessible pores, and total or partial collapse of the crystalline phases due to framework degradation. 39 Further, seemingly minor changes to a framework structure can drastically alter their performance during activation due to subtle changes in the metal–linker chemistry 40 or framework mechanical stability. 41,42 Attempts to improve activation methods to increase the reliability of MOF materials are therefore hindered by incomplete understanding and characterisation of these phenomena. This is particularly true of framework collapse, which is usually only identified by the loss of sample crystallinity upon activation. 39
Activation generally is done by heating the MOF material under reduced pressure in order to remove the confined fluid. 35 Direct MOF activation from the synthesis solvent – usually a polar, high boiling point compound such as dimethylformamide (DMF) – is rarely performed both due to the harsh conditions required and tendency to trigger activation-collapse. Instead, the reaction solvent is often exchanged for a more volatile alternative. 35,43,44 Solvent exchange is not universally effective, however, as the activation behaviour of specific MO

F–solvent pairs cannot be easily predicted, 41 and some MOFs even collapse upon solvent exchange. 45 Therefore, laborious trial-and-error development of activation methods are required for each new material developed. 41 Furthermore, incorporation of solvent exchange to MOF production methods adds a further processing step, with its own requirements for validation and optimisation. 44 As a result of these difficulties, investigation into the how 39 and why 41,46 of activation-collapse are essential to overcome the barriers towards cost-effective MOF scaleup.
Experimental studies into MOF activation have provided several rules of thumb for successful solvent activation, providing indicators of the underlying phenomena controlling activation-collapse. Lower surface tension and more volatile solvents such as acetone, 41 dichloromethane, 44 and hexane 39 are recommended over higher surface tension, less volatile alternatives ( Tables 1 and S1 † ). 37 In terms of the framework components, overly long and rigid linkers are discouraged, 41 as they may enable larger solvent phases to form with greater associated capillary stress. Similarly, twisted 41 or flexibile 47 linkers can lead to mechanical torsion in the metal–ligand bonds, thereby reducing the capillary stress required to break metal–ligand bonds. Beyond these rules of thumb, some MOFs require further considerations to prevent adverse outcomes of activation. For example, MOFs containing coordinatively unsaturated metal sites require solvent–metal coordination to be broken in order to activate the open metal sites, 48 and flexible MOFs can behave differently after activation depending on both crystal size and the activation solvent used. 49
These rules of thumb are largely founded on the theory that vaporisation of the solvent forms a vapor–liquid interface within the MOF, and that the associated surface tension creates capillary stresses on the framework which are strong enough to mechanically destroy the material. 35,38,44,46,50 This theory of capillary stress-led collapse has been corroborated by the successes of activation procedures avoiding the liquid–gas phase transition through the use of sublimation 51 or supercritical fluids. 52 However, to our knowledge these driving forces have yet to be confirmed theoretically and absence of theoretical insight prevents the generation of deeper understanding of key solvent and framework features driving activation-collapse. Furthermore, development of models to describe MOF activation would enable computational prediction of new activation protocols, reducing experimental overhead during materials discovery.
In this study, we comput

ationally investigate MOF activation-collapse to assess the empirical guidelines developed to prevent collapse and generate algorithms for a priori prediction of collapse (or lack thereof) during activation. Treating solvent activation as a fluid desorption problem, we apply commonly used grand canonical Monte Carlo (GCMC) techniques to investigate this process. We take advantage of transition matrix Monte Carlo (TMMC) 53 simulation algorithms to evenly sample the entire potential energy landscape for the activation of each specific MOF–solvent pair. TMMC is a technique widely used to model phase coexistence behaviour of both bulk 54,55 and confined fluids, 56 and has been applied to simulate methane in MOFs at subcritical temperatures 57 and to screen different process conditions. 58 However, to the best of our knowledge this is the first time that phase behaviour of confined organic solvents is studied using TMMC.
In this paper, we use the Zn 4 O-based IRMOF (isoreticular metal–organic frameworks) 59,60 family as exemplar materials. These MOFs have the same framework topology but by extending the length of the linkers, e.g. using biphenyldicarboxylate (IRMOF-10) instead of benzenedicarboxylate (IRMOF-1), the cavity diameter increases from ca. 12 to 17 Å and the window diameter between cavities from ca. 8 to 11 Å. Alternatively, the window diameter can be artificially reduced by adding bulky side chains to the linker molecules. We simulate the energetics of desorption as a function of solvent and framework properties, providing clear mechanistic explanation for the phenomenon and hence tools to aid synthetic route planning for experimental researchers.
GCMC simulations were performed using the DLMONTE 2.07 simulation package 61 (available online at https://gitlab.com/dl_monte ), using the dlmontepython package for simulation setup. 62 Simulation postprocessing was performed in python using the Atomic Simulation Environment (ASE) package, 63 and visualisation was performed in Paraview. 64
IRMOF models were taken from the Cambridge Structural Database, 65 with Mulliken partial charges 66 calculated using the DFTB + software. 67 The DFTB3 method 68 was employed using the 3ob-3-1 parameter set. 69 Full details of the calculations and sample input files/results are available online at ( https://github.