The role of proton transfer in multicomponent crystals of pyridine derivative with carboxylic acids

Cvetkovski, Aleksandar and Drakalska, Elena (2019) The role of proton transfer in multicomponent crystals of pyridine derivative with carboxylic acids. In: 10th Crystal Forms Conventions at Bologna, Italy, 09-11 June 2019, Bologna, Italy.

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The estimation of the extent of proton transfer between proton donor/electron acceptors and proton acceptor/electron donor moieties, both in intra- and inter-molecular cases, can be considered an emerging approach in crystal engineering, aimed at predicting the strength and the nature of hydrogen bonding interactions.1 This is particular important in the field of pharmaceutical cocrystals, due to the presence of aromatic base (e.g. pyridine) and/or carboxylic acid functionalities in many compounds of pharmaceutical relevance2,3. In general terms, shared proton between unprotonated pyridine and carboxylic group leads to neutral co-crystal formation, while completely transferred proton, associated with the formation of charge-assisted H bonds between carboxylate anion and pyridinium cation, leads to a molecular salt 4,5. To predict whether multicomponent systems in solution would co-crystallize as molecular salts or neutral co-crystals, the evaluation of ΔpKa = pKa(protonated base) − pKa(acid) could be of help: according to the so-called “rule of three”, a salt is expected if the ΔpKa (pKa–(base) – pKa(acid)) is greater than 2 or 3 units, while the formation of a cocrystals is observed if the ΔpKa is smaller than 0 1,6.
The present case study deals with the formation of molecular salts/ co-crystals containing pyridoxine, the alcohol derivative of pyridine, well known as vitamin B6, that is widely used both in therapy and food supplementation, and aromatic acids or other coformers from the FDA-GRAS (Generally Accepted as Safe for Food Additives by the Food &Drug Administration) list 2,3.
[1] S. L. Childs, G. P. Stahly, A., Park, Mol. Pharmaceutics 2007, 4 (3), 323–338
[2] A., Cvetkovski, V., Ferretti, V., Bertolasi, Acta Cryst. 2017, C73, 1064–1070
[3] A., Cvetkovski, V. Bertolasi, V. Ferretti, Acta Cryst. 2016. B72, 326–334.
[4] A., Lemmerer, S. Govindraju, M. Johnston, X. K.L. Savig, CrystEngComm, 2015, 17, 3591–3595
[5] V. Stilinović, , B. Kaitner, Cryst.GrowthDes. 2012,,12, 5763–5772
[6] P. Gilli, L. Pretto, V. Bertolasi, G. Gilli, Acc. Chem. Res., 2009, 42, 33–44

Item Type: Conference or Workshop Item (Poster)
Subjects: Medical and Health Sciences > Basic medicine
Engineering and Technology > Chemical engineering
Natural sciences > Chemical sciences
Engineering and Technology > Materials engineering
Engineering and Technology > Nano-technology
Divisions: Faculty of Medical Science
Depositing User: Aleksandar Cvetkovski
Date Deposited: 12 Dec 2019 10:01
Last Modified: 12 Dec 2019 10:01

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