Intermolecular interactions, regioselectivity, and biological activity of l-ascorbic acid, nicotinic acid and their cocrystal†

The systems of intermolecular interactions, including hydrogen bonds, in the crystal structures of the cocrystal of L-ascorbic (L-Asc) and nicotinic (Nic) acids and individual coformers are considered, and the hemolytic and cytotoxic activities of these compounds are studied in vitro. The influence of conformational differences of L-Asc molecules (total effective charge) on the formation of a network of H-bonds in the supramolecular structure of pristine L-Asc is revealed. Calculation of regioselectivity descriptors shows that the conformer of the L-Asc molecule in the L-AscNic cocrystal has higher activity compared to conformer molecules of the pristine L-Asc. No hemolysis caused by the solutions of tested acids and L-AscNic is shown. Selective cytotoxicity (antimetabolic effect according to the MTT test) of solutions of L-AscNic cocrystals against a 72-hour culture of MCF-7 breast cancer cell line versus healthy cells (mesenchymal stem cells and embryonic fibroblasts) is revealed. The possible relationship between the initial conformational state of the L-Asc molecules in the composition/structure of the studied solid compounds and the biological activity of solutions of these compounds requires further studies.