Polymorphism in Pyridine-2,6-dicarboxamides: The Role of Molecular Conformation in Hydrate Formation

Abstract

Carboxamide groups are interesting models of study in crystal engineering as they can be hydrogen-bond acceptors and donors. In this sense, organic molecules containing carboxamide groups could act as acceptors for water molecules, enabling hydrate formation. To study amide-based hydrate formation, a series of crystal structures of pyridine-2,6-dicarboxamides (carboxamide groups are −C­(O)-NH-R, where R = (1) CH2CHPh2, (3) CH2CH2Ph, (4) CH2Ph, (5) Ph-4-F, (6) Ph-4-Cl, (7) Ph-4-Br, and (8) naphth-1-yl) were chosen. A similar compound containing benzene 1,3-dicarboxamide substituted (2) was also included. Compounds 1 and 3–8 presented a structure with folded molecular conformation, where the amide chains showed the two NH groups positioned between both chains. Compound 2 had a linear molecular structure, where the amide chains were distant from each other. Compounds 1 and 3 presented hydrate phases (1:1), with 1 showing three polymorphic phases. Compounds 2 and 4–8 had anhydrous crystalline phases. Crystallization mechanisms of compounds 1–8 were proposed using the supramolecular cluster as demarcation and corroborated with the concentration-dependent 1H NMR experiments. Our findings enabled us to propose the stages in which each polymorph was formed, and the proposed crystallization mechanisms presented as first-stage stacking molecules for 1I-1II and 4–8 (one-dimensional nuclei), two-dimensional growth for 2, and dimer formation for 1III and 3. QTAIM analysis was used for a more detailed evaluation of intermolecular interaction contributions. The steric hindrance caused by the aryl groups is the possible reason for the greatest difficulty in forming hydrates for compounds 4–8. The water molecules in 1I-1III and 3 occupy the cavity formed by the organic molecules since the early crystallization stage. In this sense, it was possible to contribute insights regarding the influences between molecular conformation and the formation of hydrate structures.

[2]Rotaxane Solvates: Insights into the Presence of Solvents in the Crystal Lattice

“…Similarly, [2]­rotaxanes with a molecular weight above 1150 g mol –1 tend to crystallize with N > 2 (e.g., 13 , 14 , and 20 ). Another feature is that rotaxane solvates typically do not crystallize with solvent molecules at centers of symmetrywith few exceptionsas observed for other organic molecules. ,, …”

“…Another feature is that rotaxane solvates typically do not crystallize with solvent molecules at centers of symmetry�with few exceptions 9 �as observed for other organic molecules. 2,28,53 In this study, we employed the demarcation tool of the supramolecular cluster to obtain information about the crystallization process and the role of solvates and hydrates. The supramolecular cluster considers the smallest portion of the crystal, which has all information related to the stabilization energies between molecules and the topological complementarity concerning the contact areas between molecules (more details regarding the supramolecular cluster demarcation can be found in the Supporting Information).…”