Naslov
Design and crystal structures of novel lamotrigine cocrystals

Autori
Lekšić, E ; Pavlović, G ; Meštrović, E

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Congress of the International Union of Crystallography-Book of Abstracts. Acta Cryst. (2011) A67, C319. / - , 2011, C319-C319

Skup
XII Congress of the International Union of Crystallography

Mjesto i datum
Madrid, Španjolska, 22.08.2011. - 30.08.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cocrystal; lamotrigine; synthon

Sažetak
Design of cocrystals is conducted with detailed examination of selected API (Active Pharmaceutical Ingredient) molecular fragments that can be involved in supramolecular assemblies as well as with analysing similar structures available in crystallographic data bases. Exploring the potential of cocrystal formation contributes for better understanding the basic principles of supramolecular chemistry. In this work, lamotrigine, an antiepileptic drug was chosen as a model drug to design and prepare cocrystals on the basis of the synthon types and interactions found in its crystalline structures of salts and solvates. Due to its basicity, nitrogen N2 atom of triazine ring is always protonated in lamotrigine salts. It is well known that the N-H×××N hydrogen bonds between amino groups and the N2 triazine nitrogen atom form an dimer in lamotrigine structure itself [1]. These dimers are usually further connected via N-H×××O hydrogen bonds between another N-H amino group and oxygen atoms of oxygen containing solvate molecules into more complex hydrogen-bonded rings. These synthons along with the presence of clorine atoms in lamotrigine molecule are considered as models in design of targeted lamotrigine cocrystals. In that context, four cocrystal former molecules are chosen for lamotrigine cocrystal preparation: phthalimide (1) and analogous pyromellitic diimide (2), caffeine (3) and isophthaldehyde (4) on the basis of their stereochemically disposable proton donors (N-H) and proton acceptors (keto groups). In cocrystal structures with (1), (2) and (3) molecules, the lamotrigine N-H groups and the triazine N2 atom participate into hydrogen bond formation mutually via N-H×××N hydrogen bonds and with cocrystal molecule via N-H×××O=C bonds. The presence of the Cl×××O short contacts in (2), (3) and (4) structures has been confirmed.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA