*2.5. Differential Scanning Calorimetry (DSC) and Thermogravimetric (TG) Measurements*

DSC and TG measurements were carried out with the Thermo plus EVO2-DSC 8230 and the Thermo plus EVO2-TG8120 TG-DTA, respectively (Rigaku). The DSC sample (~3 mg) was placed in an aluminum-crimped pan, measured at a speed of 5 ◦C/min from 25 to 250 ◦C under nitrogen gas (flow rate = 50 mL/min. The TG sample (~10 mg) was

placed into an aluminum-open pan, respectively, and measured at a speed of 5 ◦C/min from 25 to 250 ◦C under nitrogen gas (flow rate = 50 mL/min for DPA, PA and 100 mL/min for DPA\_PA salt). *2.6. Fourier Transform Infrared Spectroscopy (FT-IR)*  The infrared spectra of samples were obtained using FT-IR (FT-IR-4200 spectrometer, JASCO Co., Tokyo, Japan) with an attenuated total reflection (ATR) unit (ATR-PRO 670H-

mg) was placed in an aluminum-crimped pan, measured at a speed of 5 °C/min from 25 to 250 °C under nitrogen gas (flow rate = 50 mL/min. The TG sample (~10 mg) was placed into an aluminum-open pan, respectively, and measured at a speed of 5 °C/min from 25 to 250 °C under nitrogen gas (flow rate = 50 mL/min for DPA, PA and 100 mL/min for

#### *2.6. Fourier Transform Infrared Spectroscopy (FT-IR)* S, JASCO Co.). The spectrum recorded represents an average of 64 scans obtained with a

*Crystals* **2021**, *11*, x FOR PEER REVIEW 4 of 20

The infrared spectra of samples were obtained using FT-IR (FT-IR-4200 spectrometer, JASCO Co., Tokyo, Japan) with an attenuated total reflection (ATR) unit (ATR-PRO 670H-S, JASCO Co.). The spectrum recorded represents an average of 64 scans obtained with a resolution of 4 cm−<sup>1</sup> at room temperature. The spectra were collected in the wavenumber ranging from 4000 to 400 cm−<sup>1</sup> . The internal reflectance element used in this study was a diamond trapezoid having 45◦ entrance and exit faces. resolution of 4 cm−1 at room temperature. The spectra were collected in the wavenumber ranging from 4000 to 400 cm−1. The internal reflectance element used in this study was a diamond trapezoid having 45° entrance and exit faces. **3. Results and Discussion**  *3.1. Crystal Structure of DPA* 

#### **3. Results and Discussion** Suitable crystals of DPA were grown from the cyclohexane solvent by slow evapora-

DPA\_PA salt).

#### *3.1. Crystal Structure of DPA* tion at ambient conditions. Its structure was determined by single crystal X-ray diffraction

Suitable crystals of DPA were grown from the cyclohexane solvent by slow evaporation at ambient conditions. Its structure was determined by single crystal X-ray diffraction and showed that it crystalized in monoclinic centrosymmetric space group *P*21/*n*, containing two symmetry independent molecules (designated as A and B molecules) in the asymmetric unit and which have opposite configuration. The Oak Ridge Thermal Ellipsoid Plot (ORTEP) of DPA is shown in Figure 2a. In the structural overlay studies two conformers which, having similar configuration, are used and reveal a minor conformational difference at the amide group, phenyl and 2-pyridine moieties, whereas difference at *iso*-propyl moiety was found to be more as shown in Figure 2b. Furthermore, interestingly in both molecules A and B of DPA, the phenyl ring moiety is nearly coplanar with the chain moiety (excluding the *iso*-propyl moiety) whereas the 2-pyridine moiety is oriented nearly perpendicular to the planar part as shown in Figure 2b. The crystallographic information and geometrical parameters for the hydrogen bonding interaction are summarized in Tables 1 and 2. and showed that it crystalized in monoclinic centrosymmetric space group *P*21/*n*, containing two symmetry independent molecules (designated as A and B molecules) in the asymmetric unit and which have opposite configuration. The Oak Ridge Thermal Ellipsoid Plot (ORTEP) of DPA is shown in Figure 2a. In the structural overlay studies two conformers which, having similar configuration, are used and reveal a minor conformational difference at the amide group, phenyl and 2-pyridine moieties, whereas difference at *iso*-propyl moiety was found to be more as shown in Figure 2b. Furthermore, interestingly in both molecules A and B of DPA, the phenyl ring moiety is nearly coplanar with the chain moiety (excluding the *iso*-propyl moiety) whereas the 2-pyridine moiety is oriented nearly perpendicular to the planar part as shown in Figure 2b. The crystallographic information and geometrical parameters for the hydrogen bonding interaction are summarized in Tables 1 and 2.

**Figure 2.** (**a**) The Oak Ridge Thermal Ellipsoid Plot (ORTEP) diagram of Molecule A and Molecule B of DPA, showing the atom numbering scheme in. Thermal ellipsoid drawn at 50% probability level, and H-atoms are shown as small spheres with arbitrary radii. Both symmetry independent molecules A and B in the asymmetric unit display the N-H∙∙∙N intramolecular hydrogen bond in S11(6) motif; (**b**) Structural overlay of two conformers in DPA which, having similar configuration, reveal considerable conformational differences at the *iso*-propyl moiety present on the tertiary N-atom of chain moiety. Molecule B**`** is inversion symmetry related to Molecule B. **Figure 2.** (**a**) The Oak Ridge Thermal Ellipsoid Plot (ORTEP) diagram of Molecule A and Molecule B of DPA, showing the atom numbering scheme in. Thermal ellipsoid drawn at 50% probability level, and H-atoms are shown as small spheres with arbitrary radii. Both symmetry independent molecules A and B in the asymmetric unit display the N-H···N intramolecular hydrogen bond in S<sup>1</sup> 1 (6) motif; (**b**) Structural overlay of two conformers in DPA which, having similar configuration, reveal considerable conformational differences at the *iso*-propyl moiety present on the tertiary N-atom of chain moiety. Molecule B**'** is inversion symmetry related to Molecule B.


**Table 1.** Crystallographic data table for the DPA and DPA\_PA salt.

**Table 2.** Geometrical parameters of the hydrogen bond interaction in DPA and DPA\_PA salt.



**Table 2.** *Cont.*

*Crystals* **2021**, *11*, x FOR PEER REVIEW 6 of 20

In the crystal structure of pure DPA, two closely associated DPA molecules, that is, molecules A and B aggregate via amide homodimer through N–H···O hydrogen bonds, namely N2-H2A···O2, N5-H4A···O1 hydrogen bonds involving amide hydrogen N–H and amide C=O oxygen from both DPA molecules resulting R<sup>2</sup> <sup>2</sup>(8) ring motifs involving two donor and two acceptor atoms. Whereas second amide hydrogen N–H in both symmetry independent DPA molecules formed an intramolecular N-H···N hydrogen bond with the Nnitrogen atom of 2-pyridine moiety in S<sup>1</sup> <sup>1</sup>(6) motif, namely N2-H2B···N1 and N5-H4B···N4, and hence it controls orientation of 2-pyridine moiety of DPA molecules in the crystal structure as shown in the Figure 3. In the crystal structure of pure DPA, two closely associated DPA molecules, that is, molecules A and B aggregate via amide homodimer through N–H∙∙∙O hydrogen bonds, namely N2-H2A∙∙∙O2, N5-H4A∙∙∙O1 hydrogen bonds involving amide hydrogen N–H and amide C=O oxygen from both DPA molecules resulting R22(8) ring motifs involving two donor and two acceptor atoms. Whereas second amide hydrogen N–H in both symmetry independent DPA molecules formed an intramolecular N-H∙∙∙N hydrogen bond with the Nnitrogen atom of 2-pyridine moiety in S11(6) motif, namely N2-H2B∙∙∙N1 and N5-H4B∙∙∙N4, and hence it controls orientation of 2-pyridine moiety of DPA molecules in the crystal structure as shown in the Figure 3.

**Figure 3.** Two closely associated molecules of DPA, that is, molecules A and B involved in ring formation (basic dimeric unit) through an N–H∙∙∙O hydrogen bond and the resulting R22(8) ring motifs. A second amide hydrogen N–H engaged in intramolecular hydrogen bonding with the Natom of the 2-pyridine moiety in S11(6) motif. Dotted lines indicate the non-covalent interaction (hydrogen atoms not involved in the hydrogen bonding were removed for clarity). **Figure 3.** Two closely associated molecules of DPA, that is, molecules A and B involved in ring formation (basic dimeric unit) through an N–H···O hydrogen bond and the resulting R<sup>2</sup> 2 (8) ring motifs. A second amide hydrogen N–H engaged in intramolecular hydrogen bonding with the N-atom of the 2-pyridine moiety in S<sup>1</sup> 1 (6) motif. Dotted lines indicate the non-covalent interaction (hydrogen atoms not involved in the hydrogen bonding were removed for clarity).

Packing of the dimeric unit down the *c*-axis, resulting in a 1-D chain of the dimeric unit along the *ab*-diagonal, wherein dimeric units of DPA are linked through C-H···O and C-H···π interaction, containing alternate arrangements of vertically and horizontally oriented dimeric units. In this association C10-H10, C11-H11 hydrogen of 2-pyridine moiety of molecule A and C32-H32 hydrogen of 2-pyridine moiety, and C42-H42A hydrogen of *iso*-propyl moiety of molecules B are involved in the alternate C10-H10···O2, C11- H11···Cg4, and C32-H32···Cg2, C42-H42A···Cg4 interaction shown Figure 4a. The dimeric unit assembled helically along the *b*-axis to form a helical chain of the dimeric unit as shown in Figure 4b and dimeric unit along the *b*-axis linked through longer and roughly linear C2-H2···O2 (H2···O2, 2.67 Å, Angle 165.71◦ ) interaction. Packing of the dimeric unit down the *c*-axis, resulting in a 1-D chain of the dimeric unit along the *ab*-diagonal, wherein dimeric units of DPA are linked through C-H∙∙∙O and C-H∙∙∙π interaction, containing alternate arrangements of vertically and horizontally oriented dimeric units. In this association C10-H10, C11-H11 hydrogen of 2-pyridine moiety of molecule A and C32-H32 hydrogen of 2-pyridine moiety, and C42-H42A hydrogen of *iso*-propyl moiety of molecules B are involved in the alternate C10-H10∙∙∙O2, C11-H11∙∙∙Cg4, and C32- H32∙∙∙Cg2, C42-H42A∙∙∙Cg4 interaction shown Figure 4a. The dimeric unit assembled helically along the *b*-axis to form a helical chain of the dimeric unit as shown in Figure 4b and dimeric unit along the *b*-axis linked through longer and roughly linear C2-H2∙∙∙O2 (H2∙∙∙O2, 2.67 Å, Angle 165.71°) interaction.

**Figure 4.** (**a**) Packing view of the dimeric unit down the *c*-axis, resulting in a 1-D chain of dimeric unit containing an alternate arrangement of vertically and horizontally oriented dimeric unit along the *ab*-diagonal; they are associated through alternate C10-H10∙∙∙O2, C11-H11∙∙∙Cg4, and C32-H32∙∙∙Cg2, C42-H42A∙∙∙Cg4 interaction and (**b**) Packing of dimeric unit along the *b*-axis resulting in a helical chain of the dimeric unit, linked through C2-H2∙∙∙O2 interaction. **Figure 4.** (**a**) Packing view of the dimeric unit down the *c*-axis, resulting in a 1-D chain of dimeric unit containing an alternate arrangement of vertically and horizontally oriented dimeric unit along the *ab*-diagonal; they are associated through alternate C10-H10···O2, C11-H11···Cg4, and C32-H32···Cg2, C42-H42A···Cg4 interaction and (**b**) Packing of dimeric unit along the *b*-axis resulting in a helical chain of the dimeric unit, linked through C2-H2···O2 interaction.

Combining the above mentioned packings resulted in the 2-D packing of the dimeric unit in the *ab*-plane, as shown Figure 5. In this packing, the neighboring helical chain of the dimeric unit packed in the *ab*-plane through the alternate C10-H10∙∙∙O2 C11-H11∙∙∙Cg4, and C32-H32∙∙∙Cg2, C42-H42A∙∙∙Cg4 interaction generate the 2-D packing of the dimeric unit in the *ab*-plane, as shown in Figure 5. Combining the above mentioned packings resulted in the 2-D packing of the dimeric unit in the *ab*-plane, as shown Figure 5. In this packing, the neighboring helical chain of the dimeric unit packed in the *ab*-plane through the alternate C10-H10···O2 C11-H11···Cg4, and C32-H32···Cg2, C42-H42A···Cg4 interaction generate the 2-D packing of the dimeric unit in the *ab*-plane, as shown in Figure 5.

Furthermore, such 2-dimensional structure of the dimeric unit assembled loosely due to the absence of strong interaction along the *c*-axis. In this direction, that is, along the *c*-axis, the 2-D network of dimeric units interact with each other by weak non-covalent interactions and hydrophobic forces between adjacent phenyl and *iso*-propyl groups and such packing of dimeric unit in the *ac*-plane creates a solvent assessable void of size 54.85 Å<sup>3</sup> per unit cell and 1.4% of unit cell volume, calculated by using contact surface from Mercury 2020, 2.0 software [54] shown in Figure 6. Crystal with assessable solvent void is recently reported in [55].

*Crystals* **2021**, *11*, x FOR PEER REVIEW 8 of 20

*Crystals* **2021**, *11*, x FOR PEER REVIEW 8 of 20

**Figure 5.** Helical 1-D chain of dimeric unit of DPA is assembled in the *ab*-plane resulting in 2-D packing. In this packing, the central 1-D dimeric unit chain of DPA molecules is associated with the neighboring dimeric chain via C-H∙∙∙O and C-H∙∙∙π interaction and the resulting tight packing in the *ab*-plane. **Figure 5.** Helical 1-D chain of dimeric unit of DPA is assembled in the *ab*-plane resulting in 2-D packing. In this packing, the central 1-D dimeric unit chain of DPA molecules is associated with the neighboring dimeric chain via C-H···O and C-H···π interaction and the resulting tight packing in the *ab*-plane. teractions and hydrophobic forces between adjacent phenyl and *iso*-propyl groups and such packing of dimeric unit in the *ac*-plane creates a solvent assessable void of size 54.85 Å3 per unit cell and 1.4% of unit cell volume, calculated by using contact surface from Mercury 2020, 2.0 software [54] shown in Figure 6. Crystal with assessable solvent void is

axis, the 2-D network of dimeric units interact with each other by weak non-covalent in-

Furthermore, such 2-dimensional structure of the dimeric unit assembled loosely due to the absence of strong interaction along the *c*-axis. In this direction, that is, along the *c*-

**Figure 6.** Neighboring 2-dimensional network of dimeric units of DPA assembled loosely via relatively weak non-covalent interaction and hydrophobic forces along the *c*-axis, resulting in 3 dimensional packing; such packing creates a solvent accessible void between them.
