Probing the structural pathway of conformational polymorph nucleation by comparing a series of α,ω-alkanedicarboxylic acids

The relationships and distinctions among a series of diacids in polymorphic outcomes and solid/solution chemistry were utilized to reveal the conformational polymorph nucleation pathway: difficulty in desolvation has a remarkable effect on the result of rearrangement and nucleation outcome.

The solubility measurement methods and results are shown in Table S1. Table S2 and S3 showed the crystallographic data of form I and form II of 6 diacids used in this work, respectively. Table S4 and S5 showed Experimental details of new structures of DA13 and DA15. PES scan of DA5 and DA11 about the rotatable bond τ 2 from -180° to 180° with τ 1 fixed at different values in solvents was presented in Fig. S1. The molecular structures of additives used in this study were shown as Fig. S2.
CCDC 1941171−1941172 (for the structures of form II of DA13 and DA15) contain the supplementary crystallographic data for this paper.

S1. Solubility Measurements
A gravimetric method was employed to determine the solubility of the stable form I of diacids in some mono-solvents (showed in Table S1) at 298.15 K. In this process, excess solid diacids and corresponding single, were added to 50 mL flasks so that to obtain the suspensions. Then the suspensions were shaken by a thermostatic bath shaker (CHY1015, Shanghai Sunny Hengping Scientific Instrument Co. Ltd., China) at a certain temperature under uncertainty of 0.1 K. And this process would last for 12 h which had been proved to be long enough to achieve solid-liquid equilibrium in preliminary experiment. After turning off the bath shaker, 5 mL of the supernatant liquor was filtered by the pre-cooled/heated syringes filters (0.22 µm) and moved into pre-weighted glass dishes as quickly as possible. Immediately, the total weight was determined. After that, the dishes were dried in a vacuum oven (DZ-2BC, Tianjin Taisite Instrument Co. Ltd., China) at T=343.15 K and their mass was periodically measured until the data remained constant, which meant that the solvent had been completely evaporated. In all above experiments, the masses were determined by an electronic balance (AB204-N, Mettler-Toledo, Switzerland) with an accuracy of ± 0.0001 g. The experiment was repeated three times for error reduction, and the result was from the average value.
The solubility of metastable form II of diacids was determined by dynamic method using the laser monitoring observation technique. At a given temperature, a fixed mass of solvent was added in the vessel with stirring. To avoid the solvent losses due to evaporation, a condenser was connected to the vessel. After the temperature of vessel was stable, a fixed amount of form II was added in the vessel.
When the solid in the vessel disappeared completely, and the intensity of the transmitted laser through the solution reached the maximal value, the maximal value of the intensity was recorded as I max . Then a small amount of form II which was accurately weighed was put into the vessel, after which the intensity of the transmitted laser decreased immediately. However, if the solution is unsaturated, the new added solid will dissolve gradually, and the maximum intensity of transmitted laser will be IUCrJ (2020). 7, doi:10.1107/S205225252000233X Supporting information, sup-2 reached at the end. The same procedure was repeated until the solution reached the saturation point.
Then the total mass of form II added to the vessel was recorded and the solubility can be calculated.
The interval of every addition was 60 min. For each measuring point, the same experiment was carried out three times.
The mole fraction solubility of diacids (x 1 ) was calculated by using Eq. (S1): Where m 1 represents the mass of solute diacids, m 2 mean the masses of solvents. M 1 and M 2 are the corresponding molecule mass of them.