Novel co-crystals of the nutraceutical sinapic acid

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Sinha, Abhijeet S.
Khandavilli, Udaya Bhaskara Rao
O'Connor, Emma L.
Deadman, Benjamin J.
Maguire, Anita R.
Lawrence, Simon E.
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The Royal Society of Chemistry
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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.