Diastereomeric salts of (S,S)-sertraline with l- and d-tartaric acids: an investigation into chiral supramolecular discrimination

Abstract

Diastereomeric salts of (S,S)-sertraline, (Srt), with L- and D-tartaric acids have been prepared and their physical–chemical properties have been analyzed. Single-crystals of these salts have been grown and characterized by X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, hot-stage microscopy, and solubility measurements. The Srt⁺ conformation proved to be critical for chiral discrimination. The L and D-tartrate anions are bound to the Srt⁺ cation resulting in the formation of non-isostructural phases. The Srt salt with L-tartaric acid (Srt–L-Ta) is anhydrous (C2, Z′ = 1) while that with D-tartaric acid (Srt–D-Ta) crystallizes as a hydrate in which water molecules bridge the cation to the anion (P2₁2₁2₁, Z′ = 1). Despite being formed by different synthons, the 3D arrangement of both salts displays structures by alternating hydrophilic and hydrophobic zones. In Srt–L-Ta, the anions are self-assembled by OH⋯COOH H-bonds to form a polar domain that attaches Srt⁺ cations via NH⋯COO⁻ ones. In hydrate Srt–L-Ta, the polar zone is due to the hydrated assembly of anions that surround the Srt⁺ cations H-bonded through the N⁺H⋯H₂O motif. The diastereomeric salt pair has different calculated densities and similar thermal stability (both degrade at 200 °C), but they differ significantly in solubility. The Srt–D-Ta salt is 1.6 times less soluble than the Srt–L-Ta one. Due to these features, these Srt salts have demonstrated the potential for the crystallization-based resolution of tartaric acid.