**2. Results**

#### *2.1. MOF Synthesis, Loading Sieved Catalysts in the Capillary Flow Reactor and Analysis of the Catalyst Bed*

All reagents were purchased from commercial sources and used without further purification. **UiO-66-14nm** (**1**), **UiO-66-200nm** (**2**), **UiO-66-540nm** (**3**), **UiO-66-NH2-14nm** (**4**), and ethyl-paraoxon were synthesized according to literature procedures (see the Supplementary Materials) [31,32].

To prepare the particles suitable for microreactor loading, the as-synthesized MOF powders were tableted for 5 min using a bench-top tablet press at 10 tons for a tablet diameter of 13 mm. The tablet was then crushed using a hand mortar and sieved. Particle sizes in the sieved fraction ranged from 45 to 125 μm and from 125 to 250 μm were collected for reactor loading. The process was repeated several times until a su fficient amount of powder in the targeted ranges was obtained. The sieved catalyst was then loaded into the 15 cm capillary tube with an internal diameter of 1.55 mm. The capillary loaded with the catalyst was secured from both sides by inserting glass wool. A quantity of catalyst ranging from 35 to 60 mg was loaded into each capillary, resulting in loaded catalyst lengths of 28 to 37 mm. The six capillary tubes prepared according to this method are summarized in Table 1. For example, reactor **1a** represents the capillary tube loaded with a 30 mm catalyst bed of 35 mg of particles, with particle size fractions between 125 and 250 μm and prepared with **UiO66\_14nm and UiO66** MOF with an average crystal size of 14 nm.


**Table 1.** Catalyst-loaded capillary reactors used in this study.

Table 2 presents the Langmuir surface area of as-synthesized MOF samples after tableting and sieving and a sample analyzed after the reaction. The surface area measurements for as-synthesized MOF was similar to what is reported in the literature [33,34]. The surface area of tableted MOF **1a** significantly decreased compared to as-synthesized **UiO66**, **1**, although no damage to the crystal structure was incurred as observed by the powder X-ray di ffraction (PXRD) patterns, which are shown in the supplementary material. A similar decrease in the surface area after the tableting and sieving process was also observed for catalyst **4a**. A significant decrease in surface area for catalysts **2a** and **3a**, with larger crystal sizes, has also been previously reported [35]. We also observed that the surface area of catalyst **1aAR** recovered after the reaction decreased compared to the surface area measured before loading, which may be due to the substrate or product being trapped in the pores of the catalyst during the flow reaction. The as-synthesized, tableted, and sieved catalysts were also analyzed by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy dispersive X-ray analysis EDX-elemental mapping and PXRD techniques. Despite the observed decrease in the surface area, these measurements showed that the structure and integrity of the particles were preserved during the flow reactions, in agreemen<sup>t</sup> with previous observations on the mechanical and chemical stability of **UiO66** MOFs. Detailed TEM, SEM, and EDX-elemental mapping and Brunauer-Emmett-Teller (BET) and PXRD analysis data are provided in the Supplementary Materials, Figures S1–S17.


**Table 2.** Langmuir surface areas of prepared **UiO66**-based MOFs.

**AR** After catalytic run.

#### *2.2. Catalyst Testing for Ethyl Paraoxon Hydrolysis and Analysis*

The experimental setup for the flow microreactor is shown in Figure 1. It consisted of a syringe pump that enabled the microreactor flow rates to be controlled. The 12 mL syringe was filled with the bu ffer solution of the 3.4 g/<sup>L</sup> (0.012 mol/L) organophosphorus agen<sup>t</sup> and connected to the reactor via capillary tubes. The reactions were conducted at di fferent temperatures by placing the microreactor in a heated water bath. The products were collected in small batches of less than 0.2 mL and the yields were measured o ffline via UV spectroscopy by comparing the absorbance of p-nitrophenoxide at 405 nm in the product mixture to the calibration curve. The calibration curve and further details about the UV analysis are provided in the Supplementary Materials, Figure S18.

**Figure 1.** Experimental testing setup and analysis. (**i**) Syringe pump, (**ii**) water bath, (**iii**) loaded MOF catalyst in a capillary flow reactor, (**iv**) collected sample in a vial, (**v**) UV–Vis spectroscopy, (**vi**) example of one of the results, including reference starting solution.

After the catalyst was loaded, the loaded microreactors were tested for a pressure drop at three flow rates of 0.5, 1, and 1.5 mL/min using water. A very high pressure drop was observed in reactors **1b** and **4b** (Table 1) with sieved particle sizes between 45 and 125 μm that resulted in catalyst particle movement and the formation of a segregated channeled catalyst bed. For reactors loaded with larger sieved particle sizes of 125 to 250 μm, the catalyst bed was stable and demonstrated reproducible performance. MOF catalyst particles larger than 125 μm were therefore tested in catalytic runs in the capillary flow reactor.

Figure 2 summarizes all of the flow reactions conducted in this study. Results are presented in terms of yield versus liquid hourly space velocity (LHSV, flow rate divided by amount of loaded catalyst). For reactor **1a** tested in an ambient temperature, yields in excess of 93% in less than 15 s were obtained, corresponding to an LHSV of 7.1 L/min/kg (a liquid flow rate of 0.25 mL/min). The yield decreased linearly as the flow rate increased. A good level of reproducibility was observed, with a yield fluctuation of ±2%. Reactor **1b**, loaded with the same MOF catalyst but a smaller particle size (with a sieved fraction between 45 and 125 μm), demonstrated a significantly lower yield (see Figure S19 in Supplementary Materials). As mentioned earlier, the catalyst bed was not stable for sieved fractions smaller than 125 μm, resulting in segregation and channeling because of the very high pressure drop.

**Figure 2.** The plot of yield vs. liquid hourly space velocity (LHSV) for reactors 1–4.

**UiO66** crystal sizes of 14, 200, and 540 nm, **1a**, **2a**, and **3a**, respectively, were tested, as shown in Figure 2. These MOFs were all prepared according to the procedure described by Morris et al., in which the average MOF particle size was controlled by the amount of acid used in the synthesis, whereby using a larger amount of acid in the MOF synthesis leads to the formation of MOFs with larger crystal size [31]. Increasing the crystal sizes decreased the yield at a given LHSV. This is consistent with the results reported in the literature. Since the reaction is considered to occur at the surface of the crystal, catalysts with a smaller crystal size will have more surface area accessible and more activity [36]. The yield trend for larger crystal sizes of 200 nm (**2a**) and 540 nm (**3a**) was different than that of **1a**, indicating that other factors influence the activity. It could be that when crystal size increases, the interparticle pore structure in the crystal aggregate is altered to reduce the accessibility of the catalytically active sites. The effect of the –NH2 group in the MOF linker on catalyst activity was also tested. As expected, the presence of the –NH2 group in the MOF resulted in a significant increase in catalyst activity, in agreemen<sup>t</sup> with prior reports [37].

The long-term stability of the catalyst under the flow conditions was tested by running the reference catalyst in reactor **1a** for 18 h at a liquid flow rate of 0.5 mL/min at 20 ◦C with periodic sampling, as shown in Figure 3. As can be seen in the figure, catalyst activity remained level throughout the testing period. This excellent stability over time suggests good potential for future practical applications of MOF catalysts in flow reactors.

**Figure 3.** Stability of reaction yield for reference case of reactor **1a** tested for 18 h at liquid flow rate of 0.5 mL/min and 20 ◦C.

#### *2.3. Catalyst Kinetic Evaluation Based on Initial Rates*

The effect of temperature on catalyst performance is shown in Figure 2 for reactor **1a**. The flow microreactor enabled multiple space times and temperatures to be easily tested. This is a significant advantage over batch reactors where each condition requires a separate reaction setup. The kinetic measurements of catalyst **1a** were found to nicely fit first-order reaction kinetics, as shown in Figure 4. Using the Arrhenius plot, the apparent activation energy was estimated as 8.8 kJ/mol. Although the response to temperature is evident in Figure 4, the process may be limited by internal mass transfer limitation, as the apparent activation energy (Ea) value could be considered low [38]. To provide conclusive answers on mass transfer limitations, a dedicated study in which various particle size ranges and loading lengths are tested at different temperatures is required.

**Figure 4.** Arrhenius plot of catalyst **1a** loaded in reactor **1**, which followed first-order reaction kinetics.

#### **3. Materials and Methods**
