Iodine salts of the pharmaceutical compound agomelatine: the effect of the symmetric H-bond on amide protonation

0465888 - FZÚ 2017 RIV GB eng J - Journal Article
Skořepová, E. - Hušák, M. - Ridvan, L. - Tkadlecová, M. - Havlíček, J. - Dušek, Michal
Iodine salts of the pharmaceutical compound agomelatine: the effect of the symmetric H-bond on amide protonation.
CrystEngComm. Roč. 18, č. 24 (2016), s. 4518-4529. ISSN 1466-8033
R&D Projects: GA ČR GA15-12653S; GA MŠMT LO1603
EU Projects: European Commission(XE) CZ.2.16/3.1.00/24510
Institutional support: RVO:68378271
Keywords : agomelatine * crystal structure * API * iodides * symmetric hydrogen bond
Subject RIV: BM - Solid Matter Physics ; Magnetism
Impact factor: 3.474, year: 2016

Three structurally different iodides of agomelatine were synthesized: agomelatine hydriodide trihydrate (AGI), agomelatine hemitriiodide (AG2I3) and agomelatine hemitriiodide iodine (AGI2). Their structures were solved from single-crystal X-ray diffraction data. In all of the structures, the agomelatine molecule was positively charged. Specifically, the amide oxygen was protonated, and in two of the structures (AG2I3 and AGI2), a symmetric hydrogen bond was formed. However, agomelatine is an amidic compound, and since amides are generally considered as neutral, in addition to SXRD, we present dat a from solid state NMR and the ΔpKa calculation to support the proton transfer and the salt formation.
Permanent Link: http://hdl.handle.net/11104/0265113