*4.3. Modified Results of Catechol Crystal Morphology in Solvent Systems*

Consistent with the experiments, the MD simulation based on the MAE model was conducted in three kinds of solvent systems: isopropanol, methyl acetate and ethyl acetate. Table 3 lists the simulated results of the six significant crystal faces in the different solvents. The negative values of *E*int, which indicate the interaction energies between the solvents and the catechol crystal faces, revealed that the solvent molecule adsorption was spontaneous because the process was exothermic. The diverse absolute values of *E*s for different crystal faces in the solvents implied that the solvents had different effects on each crystal face due to their distinct characteristics. However, ordered from largest to smallest, the |*E*s| values of the (1 0 1), (1 1 0), and (0 1 1) face were the top three in all three solvents,

which means that the interactions between the solvents and crystal faces were relatively strong on the (1 1 0), (0 1 1) and (1 0 1) faces. After correction, the absolute values of the modified attachment energy |*E'*att| were sorted as follows: (0 0 2) > (1 1 0) > (0 1 1) > (1 1 −1) > (1 0 1) > (1 0 −1) in isopropanol, (0 0 2) > (0 1 1) > (1 0 1) > (1 1 0) > (1 1 −1) > (1 0 −1) in methyl acetate, and (0 0 2) > (1 0 1) > (0 1 1) > (1 1 0) > (1 1 −1) > (1 0 −1) in ethyl acetate. Although the orders were not identical, the relatively most fast-growing (0 0 2) face disappeared in all three solvent systems with the largest |*E'*att|. Meanwhile, the (1 0 −1) face remained to take up the largest percentage of the crystal facet areas compared to the crystal morphology in vacuum: 43.87% in isopropanol and more than 70% in the other two solvents. For the crystal in methyl acetate, the (1 1 0) face had more area proportion than the (1 0 1) face due to its slower growth rate with a smaller |*E'*att| value.


**Table 3.** Simulated results of the dominant crystal faces in isopropanol, methyl acetate and ethyl acetate 1.

<sup>1</sup> All energies are in kcal mol<sup>−</sup>1.

As two or three crystal faces disappeared because of their relatively fast growth rate, the crystal morphology of catechol obviously changed in the three solvent systems, which powerfully supported the non-negligible effects of the solvents on crystal habits. In the results shown in Figure 4, the simulated crystals basically conform with the experimental ones with prismatic, fusiform or hexagonal tubular shapes in isopropanol, methyl acetate and ethyl acetate, respectively. Here we introduced the aspect ratio of the crystal as a quantitive index to describe the differences between the crystals grown from distinct solvent systems. As can be seen in Figure 4, the aspect ratio of catechol crystal was mainly determined by the areas of the (1 0 −1) face and the (1 0 1) face, so here we defined the aspect ratio as the length along the (1 0 −1) face divided by the width along the (1 0 1) face in order to summarize the unified rules of morphology change. The calculated average aspect ratios of experimental crystals are shown in Figure 5, in which the catechol crystal in isopropanol and ethyl acetate has the smallest (1.29) and the largest aspect ratio (4.95), respectively. For the convenience of downstream processes, crystal products with small aspect ratios were preferred with high flowability and unbreakable shapes. Therefore, isopropanol may be the optimal solvent for catechol crystallization among the three solvents. The obvious differences in aspect ratios may be attributed to the relative growing rate of the crystal faces in specific solvent systems, which is fundamentally related to the effects of hydrogen bond or solvent diffusion velocity. This will be discussed in the following sections.

**Figure 4.** The modified morphology with the modified attachment energy (MAE) model (on the left) and the corresponding experimental crystal habits (on the right) of catechol in (**a**) isopropanol (IPA), (**b**) methyl acetate (MAC), and (**c**) ethyl acetate (EAC).

**Figure 5.** The aspect ratios of the catechol crystals obtained from solvents.
