From Competition to Commensuration by Two Major Hydrogen-Bonding Motifs

Carboxylic acid–acid hydrogen-bonding dimer and acid–pyridine hydrogen-bonding motif are two competing supramolecular synthons that a molecule possessing both carboxylic acid and pyridine functional groups could form in the solid state. Their coexistence has been observed but for the molecules with the molar ratio of carboxylic acid and pyridine groups being greater than 1:1. In this crystal engineering study, 2-[phenyl­(propyl)­amino]­nicotinic acid with a 1:1 molar ratio of these two functional groups was discovered to have two polymorphs, in which one consists of unique hydrogen-bonded tetramer units bearing both acid–acid and acid–pyridine hydrogen-bonding motifs, while the other is composed of acid–pyridine hydrogen-bonded chains. Quantum mechanical calculations were employed to unravel the essence of the coexistence of the two vying counterparts as well as the origins of the tetramer and chain structures

From Competition to Commensuration by Two Major Hydrogen-Bonding Motifs

Carboxylic acid–acid hydrogen-bonding dimer and acid–pyridine hydrogen-bonding motif are two competing supramolecular synthons that a molecule possessing both carboxylic acid and pyridine functional groups could form in the solid state. Their coexistence has been observed but for the molecules with the molar ratio of carboxylic acid and pyridine groups being greater than 1:1. In this crystal engineering study, 2-[phenyl­(propyl)­amino]­nicotinic acid with a 1:1 molar ratio of these two functional groups was discovered to have two polymorphs, in which one consists of unique hydrogen-bonded tetramer units bearing both acid–acid and acid–pyridine hydrogen-bonding motifs, while the other is composed of acid–pyridine hydrogen-bonded chains. Quantum mechanical calculations were employed to unravel the essence of the coexistence of the two vying counterparts as well as the origins of the tetramer and chain structures

From Competition to Commensuration by Two Major Hydrogen-Bonding Motifs

Carboxylic acid–acid hydrogen-bonding dimer and acid–pyridine hydrogen-bonding motif are two competing supramolecular synthons that a molecule possessing both carboxylic acid and pyridine functional groups could form in the solid state. Their coexistence has been observed but for the molecules with the molar ratio of carboxylic acid and pyridine groups being greater than 1:1. In this crystal engineering study, 2-[phenyl­(propyl)­amino]­nicotinic acid with a 1:1 molar ratio of these two functional groups was discovered to have two polymorphs, in which one consists of unique hydrogen-bonded tetramer units bearing both acid–acid and acid–pyridine hydrogen-bonding motifs, while the other is composed of acid–pyridine hydrogen-bonded chains. Quantum mechanical calculations were employed to unravel the essence of the coexistence of the two vying counterparts as well as the origins of the tetramer and chain structures

From Competition to Commensuration by Two Major Hydrogen-Bonding Motifs

Carboxylic acid–acid hydrogen-bonding dimer and acid–pyridine hydrogen-bonding motif are two competing supramolecular synthons that a molecule possessing both carboxylic acid and pyridine functional groups could form in the solid state. Their coexistence has been observed but for the molecules with the molar ratio of carboxylic acid and pyridine groups being greater than 1:1. In this crystal engineering study, 2-[phenyl­(propyl)­amino]­nicotinic acid with a 1:1 molar ratio of these two functional groups was discovered to have two polymorphs, in which one consists of unique hydrogen-bonded tetramer units bearing both acid–acid and acid–pyridine hydrogen-bonding motifs, while the other is composed of acid–pyridine hydrogen-bonded chains. Quantum mechanical calculations were employed to unravel the essence of the coexistence of the two vying counterparts as well as the origins of the tetramer and chain structures

Two Major Pre-Nucleation Species that are Conformationally Distinct and in Equilibrium of Self-Association

To understand how solution chemistry governs polymorphic formation of organic crystals, solution NMR measurements of tolfenamic acid were conducted in ethanol. It was unveiled by chemical shift and diffusivity results that the solute molecules self-associated as dimers in solution. Further nOe (nuclear Overhauser effect) analyses indicate that a more twisted conformation became dominant over a planar conformation under the solution conditions that favored the dimer formation. This discovery is rationalized in terms of the energy balance between the conformation and intermolecular hydrogen bonding of the solute molecule, suggesting a significant role of the cooperability between a molecule’s conformation and its intermolecular interaction in determining the nucleation outcome of distinct crystal structures

From Competition to Commensuration by Two Major Hydrogen-Bonding Motifs

Carboxylic acid–acid hydrogen-bonding dimer and acid–pyridine hydrogen-bonding motif are two competing supramolecular synthons that a molecule possessing both carboxylic acid and pyridine functional groups could form in the solid state. Their coexistence has been observed but for the molecules with the molar ratio of carboxylic acid and pyridine groups being greater than 1:1. In this crystal engineering study, 2-[phenyl­(propyl)­amino]­nicotinic acid with a 1:1 molar ratio of these two functional groups was discovered to have two polymorphs, in which one consists of unique hydrogen-bonded tetramer units bearing both acid–acid and acid–pyridine hydrogen-bonding motifs, while the other is composed of acid–pyridine hydrogen-bonded chains. Quantum mechanical calculations were employed to unravel the essence of the coexistence of the two vying counterparts as well as the origins of the tetramer and chain structures

From Competition to Commensuration by Two Major Hydrogen-Bonding Motifs

Carboxylic acid–acid hydrogen-bonding dimer and acid–pyridine hydrogen-bonding motif are two competing supramolecular synthons that a molecule possessing both carboxylic acid and pyridine functional groups could form in the solid state. Their coexistence has been observed but for the molecules with the molar ratio of carboxylic acid and pyridine groups being greater than 1:1. In this crystal engineering study, 2-[phenyl­(propyl)­amino]­nicotinic acid with a 1:1 molar ratio of these two functional groups was discovered to have two polymorphs, in which one consists of unique hydrogen-bonded tetramer units bearing both acid–acid and acid–pyridine hydrogen-bonding motifs, while the other is composed of acid–pyridine hydrogen-bonded chains. Quantum mechanical calculations were employed to unravel the essence of the coexistence of the two vying counterparts as well as the origins of the tetramer and chain structures

Higher-Order Self-Assembly of Benzoic Acid in Solution

Benzoic acid forms hydrogen-bonded dimers in solution that further stack into tetramers by aromatic interactions. Both dimers and higher-order packing motifs are preserved in the resultant crystal structure. The finding hints at the significance in the hierarchy of intermolecular interactions in driving the self-association process in solution

Glycine’s pH-Dependent Polymorphism: A Perspective from Self-Association in Solution

As a simple amino acid, glycine (Gly)’s polymorphism is pH-dependent. The α form is typically obtained from aqueous solution between pH of 4 and 9, while the γ is produced at either lower or higher pH. Formation of cyclic, hydrogen-bonded dimer in water is debated as a possible cause for the formation of the α form. To further understand the pH-dependent polymorphism, our current study examined the self-association of Gly in aqueous solutions under a wide range of pH, utilizing NMR, FTIR, and electronic calculation. The results indicate that glycine molecules form open, not cyclic, hydrogen-bonded dimers in water. It is revealed that the dimerization becomes significant between pH of 4 and 8 but remains trivial at the two pH extremes. The apparent connection between the pH-dependent polymorphism and self-association in solution implies that formation of the α form is driven by the dimerization, and moreover, charged molecular species at the extreme pH facilitate stabilization of γ nuclei

Tautomeric Polymorphism of 4‑Hydroxynicotinic Acid

4-Hydroxynicotinic acid (4-HNA) was discovered to exist in the solid state as either 4-HNA or its tautomer 4-oxo-1,4-dihydropyridine-3-carboxylic acid (4-ODHPCA) in three polymorphs and two hydrates. Packing motifs differ as each of the three oxygen atoms acts as the hydrogen-bond acceptor, respectively, in the anhydrate forms, while in the hydrate forms, water molecules participate in hydrogen bonding with 4-HNA. Phase behaviors of the forms were characterized by differential scanning calorimetry (DSC), hot-stage microscopy (HSM), and thermogravimetric analysis (TGA). It was found that anhydrates I and II converted into III during heating; the two hydrate forms dehydrated at different temperatures and eventually transformed into anhydrate III, and sublimation of all five forms led to form III when the crystals were heated. Quantum mechanical calculations were performed providing further insight into the polymorphism