Dicarboxylic Acid-Based Co-Crystals of Pyridine Derivatives Involving Structure Guiding Unconventional Synthons: Experimental and Theoretical Studies

Abstract

Four co-crystals involving dicarboxylic acids and pyridine derivatives, viz. (ox)0.5(2-CNpy) (1), (adp)(4-CNpy)2 (2), (tp)(4-CNpy)2 (3) and (adp)(3-CNpy)2 (4) (ox = oxalic acid, tp = terephthalic acid, adp = adipic acid, CNpy = cyanopyridine), have been synthesized at room temperature in water medium. Crystal-structure analysis of co-crystal 1 reveals the presence of unconventional O···π(oxalic acid)-hole interaction with the C-C bond of ox moiety, along with parallel nitrile–nitrile interactions. The structural topologies of co-crystals 2–4 unfold the presence of antiparallel nitrile–nitrile interactions involving the CNpy moieties. The molecular associations involving the H-bonds and other unconventional contacts among the co-formers of the multicomponent co-crystals are analyzed using density functional theory (DFT) calculations combined with molecular electrostatic potential (MEP) surface, quantum theory of atoms-in-molecules (QTAIM) and noncovalent interaction (NCI) plot computational tools. The computational studies revealed the presence of unconventional O···π-hole interaction in 1 and the H-bonded synthons with π-stacked nitrile contacts involving CNpy moieties in co-crystals 2–4. The energetic features of the noncovalent contacts reveal the crucial roles of the H-bonding synthons and π-stacking interactions in the multicomponent compounds.

The Unconventional Noncovalent Interactions Control: Crystallographic and Theoretical Analyses of the Crystalline Structure of 1,1′‐(1‐Chloro‐4‐methoxyphenyl)dibenzene as a Case Study

“…During the optimization process, all H atoms were optimized, while the positions of other atoms were kept frozen. This method allows us to avoid geometrical rearrangement and gain a picture of the interactions as they are found in the crystal structure, while also obtain converged wavefunctions [50–52] The long‐range‐corrected wB97X‐D hybrid functional, which incorporates Grimme's D2 dispersion model, is considered well‐suited for the analysis of similar noncovalent interactions [53–55] . The validated frequency calculations confirm the stability of the optimized structures as true minima by exhibiting absence of imaginary frequencies.…”

Crystal Structure, Quantum Chemical, Hirshfeld Surface and Molecular Docking of Organic Molecular Salt: 2‐Amino‐5‐Chloropyridinium‐2,4‐Dihydroxybenzoate

“…The physicochemical properties DOI: 10.1002/crat.202300169 like solubility, stability, dissolution rate, hygroscopicity, compressibility, and bioavailability of the compounds are modified through co-crystallization or organic salt formation by non-covalent and non-ionic bonds. [3][4][5][6][7] Heterocyclic compounds with nitrogen atoms have wide applications in pharmacological and biological areas. The 2-aminopyridine and its derivatives were the intermediates in the synthesis of anti-inflammatory and non-steroidal drugs.…”