Two isotypical disodium salts of the antihypertensive agent valsartan.

Abstract

The crystal structure of disodium valsartan 3.5-hydrate, or poly[hemiheptaaqua[μ-5-{2-[4-({N-[(2S)-1-carboxylato-2-methylpropyl]pentanamido}methyl)phenyl]phenyl}-1H-1,2,3,4-tetrazol-1-ido]disodium], [Na₂(C₂₄H₂₇N₅O₃)(H₂O)_3.5]_n (1), was determined using powder X-ray diffraction data. Recrystallization of this substance from an ethanol-acetonitrile (1:1 v/v) mixture afforded disodium valsartan 2.67-hydrate ethanol 0.33-solvate, [Na₂(C₂₄H₂₇N₅O₃)(C₂H₅OH)_0.33(H₂O)_2.67]_n (2), with partially occupied ethanol and water positions. The crystal structure of 2 was studied using synchrotron radiation and refined as a two-component twin. The solids were found to be isotypical with four cations and two anions occupying equivalent positions (Z' = 2). The difference in the number of solvent molecules affects the coordination environment of Na2 and Na3 (Na2NO₅ and Na3NO₅ in 1, and NaNO₄/NaNO₅ for both atoms in 2 due to solvent disorder), while two other sodium ions maintain the NaN₂O₃ coordination. Valsartan acts as a dianion with both tetrazolyl and carboxyl groups deprotonated. The anions interact with sodium cations through the carboxyl, tetrazolyl and oxo groups as both bridging and bridging-chelating ligands. Bridging anions and water molecules connect both structures into infinite two-dimensional layers. The surface of these layers is hydrophobic due to the coating of alkyl and aryl groups. Numerous O-H...O and O-H...N hydrogen bonds are observed within the layers.