Oxalic Acid, a Versatile Coformer for Multicomponent Forms with 9-Ethyladenine

Abstract

Six new multicomponent solids of 9-ethyladenine and oxalic acid have been detected and characterized. The salt screening has been performed by mechanochemical and solvent crystallization processes. Single crystals of the anhydrous salts in 1:1 and 2:1 nucleobase:coformer molar ratio were obtained by solution crystallization and elucidated by single-crystal X-ray analysis. The supramolecular interactions observed in these solids have been studied using density functional theory (DFT) calculations and characterized by the quantum theory of “atoms in molecules” (QTAIM) and the noncovalent interaction plot (NCIPlot) index methods. The energies of the H-bonding networks observed in the solid state of the anhydrous salts in 1:1 and 2:1 nucleobase:coformer are reported, disclosing the strong nature of the charge assisted NH···O hydrogen bonds and also the relative importance of ancillary C–H··O H-bonds.

Multicomponent Crystals of Clozapine with Improved Solubility: A Combined Theoretical and Experimental Strategy on Coformer Screening and Structure–Property

“…In Figure S6b, CLZ-MA is a two-component crystal, while the other seven new solids are all three-component including coformers with solvent molecules (acetonitrile, ethanol, methanol, and water). CLZ-OXA1 and CLZ-OXA2 had three endothermic peaks, the second endothermic peak (191.74 and 190.09 °C) was suggested to be the loss of OXA molecules, , and the first endothermic peak (142.09 and 141.35 °C) was suggested to be the loss of solvent (acetonitrile and ethanol) molecules. The endothermic peaks were different with the onset endothermic temperatures of other crystals, confirming the different crystal packings.…”

Insights into structural, spectroscopic, and hydrogen bonding interaction patterns of nicotinamide–oxalic acid (form I) salt by using experimental and theoretical approaches

“…NIC has proven to be potentially safe and tolerable in humans ( Irie et al, 2020 ; Liao et al, 2021 ). Oxalic acid (OXA) is used in pharmaceutical salt preparation, and it has shown good tolerability and low toxicity ( Benito et al, 2022a ). Its main sources are plants, vegetables, fruits, nuts, and seeds ( Chukwuebuk and Chinenye, 2015 ).…”

“…Its main sources are plants, vegetables, fruits, nuts, and seeds ( Chukwuebuk and Chinenye, 2015 ). OXA consists of two carbonyl (C=O) and hydroxyl (OH) groups, in which the (C=O) group can form hydrogen bonds with a proton donor, whereas the OH group can form hydrogen bonds with a proton acceptor, and so can form salts or cocrystals easily ( Benito et al, 2022b ). The titled salt formation occurs when a proton from OXA is transferred into the nitrogen atom of the pyridine ring of NIC.…”

Multicomponent Pharmaceutical Solids

“…In M. Benito et al's paper [6], efforts were made to rationalize the nature and strength of those supramolecular interactions present in six new multicomponent systems involving the modified nucleobase 9-ethyladenine and the coformer oxalic acid. Herein, salt screening was carried out by mechanochemical and solvent crystallization techniques, yielding two molar ratios and different anhydrous/solvated forms.…”