A gold(III) complex and a tetrachloroaurate salt of the neuroepileptic drug gabapentin

Gabapentin (2-[1-(aminomethyl)cyclohexyl] acetic acid, Gp), a neuroepileptic drug, has been the subject of renewed interest in the past decade. In order to exploit the therapeutic potential of Gp several metal complexes of Gp have been investigated. In this paper we report on the preparation of a novel, unusually stable Au(III)–gabapentin complex, [Au(Gp0)Cl3], with a Au(III)―N bond, and a second product, a gabapentin–[AuCl4]− salt, both characterized by single-crystal X-ray diffraction and 2-dimensional 15N–1H NMR techniques. The crystal structure of [Au(Gp0)Cl3] clearly shows the Au―N coordination (Au―N bond 2.043(2) Å) in the hydrogen bonded dimer. In the crystal, the cyclohexyl moiety is disordered over two positions, both having a chair conformation. In solution, the 1H NMR of [Au(Gp0)Cl3] in MeOD has resonances at 2.45, 2.51, 3.05 and 3.12 ppm, that suggest that [Au(Gp0)Cl3] exists as two different isomers in solution, with the ―CH2-NH2-AuCl3 either axial or equatorial, and that on crystallization these isomers persist in the solid state.

Graphical AbstractGabapentin reacts with auric acid to form a novel Au(III)–gabapentin (Gp) complex as well as the GpH-[AuCl4] salt, the former trapped by rapid crystallization from a 1:1 ethanol:water solvent.Figure optionsDownload as PowerPoint slideResearch Highlights
► Gabapentin reacts with auric acid to form a Au(III) -Gp complex.
► An intermediate in the oxidation of Gb0 by Au(III) was trapped.
► ―CH2-NH2-AuCl3 is either ax or eq both in solution and in the solid.
► A Gb-[AuCl4] salt is also formed.
► There is an unusually stable Au―N bond in the Au(III) complex.