Modulators

Modulators are typically monotopic carboxylic acids and occasionally Brønsted bases added to nano-MOF syntheses. The intended purpose of modulators varies, but we propose that their function is to influence nano-MOF sizes by affecting linker deprotonation and arresting particle growth.44 Modulators also act to prevent particle aggregation. Although modulators produce size trends that appear complex and contradictory, their role can be rationalized in terms of the four equilibria outlined above.

When strong Brønsted bases are used as modulators, their primary role is to facilitate ligand deprotonation (eqn (1)) and enhance metal-linker complexation (eqn (3)) relative to metal-ion diffusion, thereby depleting local metal ion concentrations and forming small MOF nanocrystals. For example, nanocrystals of MFU-4 (Zn₅Cl₄(BBTA)₃) decrease in size with added lutidine or KOH.12 Similarly, when nanocrystals of NU-1000 (Zr₆(μ₃-OH)₈(OH)₈(TBAPy)₂) are prepared with the addition of 4-biphenyl-carboxylic acid, particle sizes decrease further if NaOH is added to the precursor linker solution45 Nanocrystals of MOF-5 and IR-MOF-3 (Zn₄O(TPDC)₃) require triethylamine (TEA), which become more uniform with initial addition of cetyltrimethylammonium bromide (CTAB).46 Similarly, including n-butylamine decreases nanocrystal sizes of ZIF-71 (Zn(Hdcim)₂).41 Interestingly, nanoparticles of MIL-101(Cr) (Cr₃ (H₂O)₂O[(C₆H₃)-(CO₂)₃]₂) are synthesized without any modulator by simply decreasing the amount of HF, which is used as a mineralizing agent in the traditional bulk synthesis.47–49 Adding a strong base to the reaction mixture, however, results in smaller particle sizes.50

When carboxylic acids serve as modulators, their presence can increase or decrease nano-MOF sizes depending on whether they impede linker deprotonation (eqn (1)) or act as surface capping ligands (eqn (4)). By interfering with deprotonation, they slow down metal-linker complexation (eqn (3)) relative to metal-ion diffusion, resulting in large nano-MOF sizes. On the other hand, they can terminate particle growth by acting as surface-capping ligands and produce small sizes. For example, Fig. 3A shows that while adding 0.33 equivalents of perfluorobenzoic acid generates larger MIL-101 particles relative to using no HF or modulator, the addition of more weakly acidic 4-nitrobenzoic acid, benzoic acid, 4-methoxybenzoic acid, and stearic acid decreases particle sizes with increasing modulator pK_a values.51 The less acidic the modulator, the lower the H⁺ activity in solution available to protonate linker molecules (eqn (1)).

Adding small quantities of acidic modulators decreases nano-MOF sizes until the H⁺ activity in solution reaches a threshold value that begins to interfere with linker deprotonation (eqn (1)). Further addition of acid slows metal–ligand complexation relative to metal-ion diffusion, leading to large particle sizes. For example, Fig. 3A serves as a useful comparison to the data in Fig. 3A. Both studies were conducted at similar concentrations (0.076 M versus 0.033 M) and both involve similarly strong metal–ligand bond strengths (Zr⁴⁺-carboxylate and Cr³⁺-carboxylate) but whereas 0.33 modulator equivalents were employed in Fig. 3A, much higher quantities were involved in Fig. 3B. The data show that UiO-66 (Zr₆O₆(BDC)₆) nanocrystal sizes increase with additional modulator. Interestingly, modulators with lower pK_a values produce larger particle sizes at a given amount of added modulator. For instance, 15–20 equivalents of trifluoroacetic acid (TFA) or dichloroacetic acid (DCA) produce 200 nm UiO-66 nanocrystal sizes, whereas twice that amount of acetic and formic acid are needed. Acidic modulators slow down metal–ligand complexation (eqn (3)) relative to metal-ion diffusion so that particles continue to grow. Indeed, adding thousands of equivalents of formic acid to the synthesis of UiO-66 generates single crystals hundreds of microns in diameter.52 This kinetic explanation fits many other studies in which particle sizes increase with additional acidic modulator,44,53–55 including HKUST-1 modulated by dodecanoic acid,44 PCN-224 (Zr-TCPP) with benzoic acid,53 UiO-66 with benzoic acid54 and MIL-88B-NH₂ (Fe₃O(BDC-NH₂)₃(H₂O)₂) with acetic acid.55

Concentrated reaction conditions necessitate the addition of modulator; otherwise, rapid metal-ion diffusion due to short effective pathlengths outcompetes growth termination (eqn (4)). Indeed, most nanoscale MOF syntheses rely on dilute conditions (Table S2^†). For example, synthesis of MIL-101-Cr involving high concentrations (0.2 M H₂BDC) produces small particle sizes only with addition of small quantities of benzoic acid. (Fig. 3C).48 The more acidic benzoic acid has a greater effect than acetic acid on decreasing particle sizes at such high reactant concentrations, suggesting that under these reaction conditions, interfering with metal–ligand complexation is critical to kinetically trapping small MIL-101-Cr nanocrystals.

Phase purity must be considered when choosing modulator equivalents and reaction concentrations. For example, while adding few equivalents of either acetic or benzoic acid in the synthesis of MIL-101 at high concentrations results in phase-pure MIL-101 nanocrystals, greater equivalents induce the formation of mixed-phase products49 because MIL-101 and MIL-88B occupy the same reaction space, with both arising from Fe³⁺ or Cr³⁺ and trimesic acid.56 Therefore, at a benzoic acid : linker ratio of 10 : 1, only MIL-88B microcrystals form.50 Concentration plays an important role in controlling nanocrystal phase purity as well. For example, MIL-101-Cr and MIL-88B-Fe nanocrystals have been obtained with similar equivalents of acetic acid, but the synthesis of MIL-88B-Fe was an order of magnitude more dilute (Fig. 3C). Such phase transformations with variable modulator equivalents indicate the importance of nonclassical growth mechanisms.57 Similar phenomena have been observed for the phases spaces involving MIL-100-Al (Al₃·(H₂O)₂O(BTC)₂)/MIL-96-Al (Al₁₂O-(OH)₁₆(H₂O)₅(BTC)₆ MIL-110-Al (Al₈(OH)₁₂(OH)₃(H₂O)₃(BTC)₃) and NU-901 (Zr₆(μ₃-OH)₈(OH)₈(TBAPy)₂)/NU-1000.45,58,59