**3. Results and Discussion**

*3.1. Characterization*

3.1.1. SXRD Analysis

The crystal structures revealed that both ARI-SAL salt and ARI-ADI salt acetone hemisolvate were salts and the protonation occurred at the N2 atom, forming a strong charge assisted hydrogen bond formed by the strongest acceptor from the carboxylate anion interacting with strongest N+-H donor of piperazinium (see Appendix A). The crystallographic data are listed in Table 1 and the hydrogen bonding parameters are given in Table 2. The C16-H16A··· Cl1 hydrogen bonds in Table 2 correspond to the typical intramolecular interaction characteristic of the dichlorophenyl-1-piperazinyl group in all reported ARI variants [16–18].

**Table 1.** Crystallographic data of two multicomponent crystals of aripiprazole.


**ARI-SAL salt.** The ARI-SAL salt crystallized in the monoclinic P21/c space group with an aripiprazole cation, balanced by a salicylic counter-ion, in the asymmetric unit (Figure 1a). The O5 atom of salicylic anion presented positional disorder over two sites with a 0.6: 0.4 site-occupancy. ARI-SAL salt, like other lactam compounds, formed a centrosymmetric N1-H1··· O1 dimer *<sup>R</sup>*<sup>2</sup> <sup>2</sup>(8) motif with its inversion-related molecule [32]. Interestingly, the dimer formed a 1D ribbon through the short Cl1··· O1 interaction, which formed another new dimeric substructure (Figure 2a). Furthermore, the dimer units were arranged helically into the three-dimensional network (Figure 2b) by the bifurcated N-H··· O hydrogen bonds (N2 +-H2··· O3- and N2-H2··· O4 hydrogen bond) and two weaker C-H··· O interactions (C27-H27··· O1 and C17-H17A··· O5 hydrogen bond), which generated two types of helices propagated along the b axis (Figure 2c,d).


**Table 2.** Main hydrogen bonding parameters of two multicomponent crystals of ARI.

**Figure 1.** The molecular structures of two ARI multicomponent crystals with displacement ellipsoids drawn at the 30% probability level: (**a**) ARI-SAL salt; (**b**) ARI-ADI salt acetone hemisolvate.

**ARI-ADI salt acetone hemisolvate.** The ARI-ADI salt acetone hemisolvate crystallized in the triclinic P-1 space group. The ORTEP diagram contained an aripiprazole cation, half of an adipic acid counter-ion (bisected by an inversion center), and half of an acetone molecule (Figure 1b). The solvent acetone molecule was disordered with a position occupancy of 0.5 due to the location on the symmetric center, and acted as a filler in spatial network. The centrosymmetric N1-H1··· O1 dimer *<sup>R</sup>*<sup>2</sup> <sup>2</sup>(8) motif with its inversion-related molecule also can be found and formed a 1D ribbon by the strongest charged N2 +-H2··· O3 hydrogen bond (Figure 3a). The 1D ribbon interacted with its adjacent ribbon and then formed a 2D sheet through a C15-H15A··· Cl1 hydrogen bond (Figure 3b). Finally, the 2D sheets were arranged into the three-dimensional network by a weak C11-H11A··· π hydrogen bond (Figure 3c).

**Figure 2.** Packing diagrams of ARI-SAL salt: (**a**) the 1D ribbon was formed by N1-H1··· O1 hydrogen bond and short Cl1··· O1 interaction; (**b**) packing diagram for ARI-SAL salt viewed down the b axis and the green dashed wireframe indicates two different types of helices; (**c**) the type-1 helix was propagated by the bifurcated N-H··· O hydrogen bond and weaker C27-H27··· O1 interactions; (**d**) the type-2 helix was propagated by the bifurcated N-H··· O hydrogen bond and C17-H17A··· O5 interactions (only a partial aripiprazole molecule was drawn for clarity).

**Figure 3.** Packing diagrams of ARI-ADI salt acetone hemisolvate: (**a**) the 1D ribbon formed by N1-H1··· O1 and N2-H2··· O3 hydrogen bond; (**b**) the 2D sheet formed by C15-H15A··· Cl1 hydrogen bond; (**c**) packing diagram for ARI-ADI salt acetone hemisolvate formed by C11-H11A··· Cg hydrogen bond.
