Hierarchy of Supramolecular Synthons: Persistent Carboxylic Acid···Pyridine Hydrogen Bonds in Cocrystals That also Contain a Hydroxyl Moiety

Abstract

A Cambridge Structural Database (CSD) analysis was conducted in order to evaluate the hierarchy of supramolecular heterosynthons that involve two of the most relevant functional groups in the context of active pharmaceutical ingredients, carboxylic acids and alcohols, in competitive environments. The study revealed that 34% of the 5690 molecular carboxylic acid entries and 26% of the 25 035 molecular alcohol entries form supramolecular homosynthons, whereas the remaining entries form supramolecular heterosynthons with other functional groups, in particular Narom, CONH2, C−O−C, C═O, and chloride anions. Further refinement of this raw data revealed the following: 98% occurrence of the COOH···Narom supramolecular heterosynthon in the 126 crystal structures that contain acid and pyridine moieties in the absence of other hydrogen bond donors or acceptors; and 78% occurrence of the OH···Narom supramolecular heterosynthon in 228 crystal structures that contain hydroxyl and pyridine moieties (excluding intramolec...