Molecular structure and spectroscopic studies of (−)-cytisine salt with (+)-tartaric acid

Abstract

Why the tartrate salt of (−)-cytisine? Just because tartrate anion belongs to the group of anions that are the most often used as active pharmaceutical ingredients (APIs) of category I, according to the Orange Book, and it has been already established as a safe counterion. The salt formation is the most common and effective way for modulating physical properties of drugs and increasing solubility of potential drugs. Formation of an appropriate salt can improve the overall therapeutic and pharmaceutical effects of active pharmaceutical ingredients (APIs) in this case (−)-cytisine. The main purpose of this study was to determine the structural properties of a new cytisine salt. Cytisine is natural alkaloid and a well-known smoking cessation medication because it acts as a partial nicotinic acetylcholine receptor agonist. Because solid-state form of active pharmaceutical ingredients (APIs) can be critical for design and development of a new pharmaceutical formulation, therefore, the new salt of (−)-cytisine with L-(+)-tartaric acid was characterized using structural and spectroscopic methods: single crystal X-ray diffraction, FT-IR, 1H NMR, 13C NMR. The crystal structure is stabilized by a number of OH···−OOC, N+−H···−OOC and OH···O hydrogen bonds, in addition to van der Waals interactions. The semi-tartrate anions are joined by the strong OH⋯O hydrogen bond with an O⋯O distance of 2.502(4) Å into chains linked by one water molecule, while the other water molecule acts as a bridge between chains of the semi-tartrate anions.