A cocrystal of L-ascorbic acid with picolinic acid: the role of O—H...O, N—H...O and C—H...O hydrogen bonds and L-ascorbic acid conformation in structure stabilization

Abstract

A new 1:1 cocrystal (L-Asc–Pic) of L-ascorbic acid (vitamin C) with picolinic acid was prepared as a powder and as single crystals. The crystal structure was solved and refined from single-crystal X-ray diffraction (SCXRD) data collected at 293 (2) and 100 (2) K. The samples of the L-Asc–Pic cocrystal were characterized by elemental (HCNS) analysis and titrimetric methods, TG/DTG/DSC, and IR and Raman spectroscopy. The asymmetric unit comprises a picolinic acid zwitterion and an L-ascorbic acid molecule. The stabilization energy of intermolecular interactions involving hydrogen bonds, the vibrational spectrum and the energies of the frontier molecular orbitals were calculated using the GAUSSIAN09 and the CrystalExplorer17 programs. The charge distribution on the atoms of the L-Asc–Pic cocrystal, L-ascorbic acid itself and its 12 known cocrystals (structures from Version 5.40 of the Cambridge Structural Database) were calculated by the methods of Mulliken, Voronoi and Hirshfeld charge analyses (ADF) at the bp86/TZ2P+ level of theory. The total effective charges and conformations of the L-ascorbic acid molecules in the new and previously reported cocrystals were compared with those of the two symmetry-independent molecules in the crystals of L-ascorbic acid. A correlation between molecular conformation and its effective charge is discussed.

Novel Ascorbic Acid Co-Crystal Formulations for Improved Stability

“…Selected bond lengths (Å) and bond angles (°) were listed in Table S1 of Supplementary Materials. 1a), similar to that reported for the co-crystal of ascorbic acid and pyridine-2-carboxylic acid [18]. The N-H in INA acted as the hydrogen bond donor, and the -C=O of VC acted as the acceptor in an infinite one-dimensional (1D) chain.…”

“…Two different intermolecular hydrogen bonds were detected in the crystal structureone between VC and INA and the other between VC itself. The VC and INA molecules were combined via synthons I and II, wherein the two enol hydroxyl groups of VC and the -COO − fragment of the zwitterion of INA were linked via two O-H•••O hydrogen bonds to form an R 2 2 (9) ring motif (Figure1a), similar to that reported for the co-crystal of ascorbic acid and pyridine-2-carboxylic acid[18]. The N-H in INA acted as the hydrogen bond donor, and the -C=O of VC acted as the acceptor in an infinite one-dimensional (1D) chain.…”

“…The two hydroxyl groups of ascorbic acid can act as both donors and acceptors for hydrogen bonds and may form hydrogen bonds with CCFs bearing carboxyl and hydroxyl groups. Although several ascorbic acid co-crystals have been reported in recent years, a systematic correlation has not been established between the co-crystal structures and the mechanical properties [18]. The co-crystals of VC with a series of CCFs containing carboxyl and hydroxyl groups, such as isonicotinoid, nicotinamide, nicotinic acid, 4,4-bispyridine, arginine, serine, and 2-amino-6-methylpyridine, have been reported before [19][20][21][22][23][24][25][26].…”

Polymorphism in the 1/1 Pterostilbene/Picolinic Acid Cocrystal

“…For instance, the relative bioavailability of quercetin/picolinic acid (coformer in neutral form) with respect to quercetin was 1.75, the apparent aqueous solubility improvement of leflunomide/picolinic acid (coformer in zwitterionic form) in 1/1 and 1/2 stoichiometries were 1.27 and 1.09 respectively, and the relative bioavailability of the hesperetin/picolinic acid (coformer in zwitterionic form) with respect to hesperetin was 1.36. This is compatible 25 cocrystal yes B PAQMEC 28 cocrystal yes B QUJQOE 29 cocrystal yes B RAHKUJ 30 cocrystal yes B NAFZAY 31 cocrystal yes C UBUFIJ 32 cocrystal no C PAQMIG 28 cocrystal no C DEQGAK 33 salt no D PICASC 34 cocrystal yes D ANIMES 35 peroxosolvate yes D BEBCAP 36 cocrystal yes D PICOLA02 37 anhydrous with the "spring and parachute" model, 38 in which a highsolubility coformer is released into the water solution, resulting in cocrystal collapse together with the dissolution of the amorphous, less soluble component of the cocrystal. Thus, the solubility of the cocrystal is directly influenced by the solubility of the coformer.…”

Design of Ascorbic Acid Eutectic Mixtures With Sugars to Inhibit Oxidative Degradation

“…Crystal structures of ASC and its cocrystals with sarcosine, betaine, l -serine, nicotinic acid, picolinic acid, isoquinoline carboxylic acid, nicotinamide, isonicotinamide, and salt with arginine are reported in the literature ( Sudhakar et al, 1980 ; Sudhakar and Vijayan, 1980 ; Goher et al, 2003 ; Kavuru et al, 2010 ; Wang et al, 2016 ; Evtushenko et al, 2020 ). Most of the cocrystal structures consist of hydrogen bonding between ene-diol of ASC with the coformers.…”