The structure and diffusion behaviour of the 1:1 copper(II) complex of ethambutol in aqueous solution

Abstract

Ethambutol (as its dihydrochloride) is a bacteriostatic drug, which is widely used as part of the Tuberculosis treatment protocol. It can also act as a ligand for various metal ions, such as copper(II), leading to complexes with potentially interesting applications in medicinal and analytical chemistry. The structure of such complexes is relevant to the question of the coordination geometry of the copper(II) ion in aqueous solution. We report a structural study of the 1:1 complex formed between ethambutol (Emb) and copper(II), using visible absorption, multinuclear NMR (1H and 13C), and EPR spectroscopies, and density functional theory (DFT) calculations. These all support a pentacoordinate structure with a distorted square pyramidal geometry involving a central Cu(II) ion coordinated by a tetradentate Emb ligand and one water molecule. The diffusion behaviour of this complex has been studied, and is compared with that of the free ligand by measuring limiting mutual diffusion coefficients for aqueous systems at 25 °C using the Taylor dispersion method. From these results, we have estimated the tracer diffusion coefficient of ethambutol in supporting solutions of copper nitrate and the limiting diffusion coefficients of the 1:1 complex formed between ethambutol and copper ion. By using the Stokes-Einstein equation, the limiting hydrodynamic radii of this complex, Rh, have also been estimated and are compared with the free Emb.