Novel co-crystals of the nutraceutical sinapic acid
Sinha, Abhijeet S.
Khandavilli, Udaya Bhaskara Rao
O'Connor, Emma L.
Deadman, Benjamin J.
Maguire, Anita R.
Lawrence, Simon E.
The Royal Society of Chemistry
Sinapic acid (SA) is a nutraceutical with known anti-oxidant, anti-microbial, anti-inflammatory, anti-cancer, and anti-anxiety properties. Novel co-crystals of SA were prepared with co-formers belonging to the category of GRAS [isonicotinic acid (INC), nicotinamide (NIA)], non-GRAS [4-pyridinecarbonitrile (PYC)], and active pharmaceutical ingredients (APIs) [6-propyl-2-thiouracil (PTU)] list of compounds. Structural study based on the X-ray crystal structures revealed the intermolecular hydrogen-bonded interactions and molecular packing. The crystal structure of sinapic acid shows the anticipated acid-acid homodimer along with discrete hydrogen bonds between the acid carbonyl and the phenolic moiety. The robust acid-acid homodimer appears to be very stable and is retained in the structures of two co-crystals (SA[middle dot]NIA and SA[middle dot]PYC). In these cases, co-crystallization occurs via intermolecular phenol O-H[three dots, centered]Naromatic hydrogen bonds between the co-formers. In the SA[middle dot]PTU[middle dot]2MeCN co-crystal the acid-acid homodimer gives way to the anticipated acid-amide heterodimer, with the phenolic moiety of SA hydrogen-bonded to acetonitrile. Attempts at obtaining the desolvated co-crystal led to lattice breakdown, thus highlighting the importance of acetonitrile in the formation of the co-crystal. Among the co-crystals examined, SA[middle dot]INC (5 weeks), SA[middle dot]NIA (8 weeks) and SA[middle dot]PYC (5 weeks) were found to be stable under accelerated humidity conditions (40 [degree]C, 75% RH), whereas SA[middle dot]PTU[middle dot]2MeCN decomposed after one week into individual components due to solvent loss.
Hydrogen bonds , 3,5-Dimethoxy-4-hydroxycinnamic acid , Cocrystals , Derivatives , Solubility , Propylthiouracil , Architectures , Stability , Phenols
SINHA, A. S., KHANDAVILLI, U. B. R., O'CONNOR, E. L., DEADMAN, B. J., MAGUIRE, A. R. & LAWRENCE, S. E. 2015. Novel co-crystals of the nutraceutical sinapic acid. CrystEngComm, 17, 4832-4841. http://dx.doi.org/10.1039/C5CE00777A