Interaction of ethambutol with transition metal ions in solution: Formation constants and stereochemical configurations of the Cu(II), Ni(II), Co(II) and Zn(II) complexes and underlying biological implications

Abstract

Ethambutol (ETB), reacts with aqueous Cu²⁺, Co²⁺ and Ni²⁺ at <em>p</em>H 11 producing [M(H₂O)₄ETB]²⁺ (M=Cu, Co) and [Ni₂(OH)₂(H₂O)₄(ETB)₂]²⁺. Nickel (II) at <em>p</em>H 9, however, forms [NiL₄ETB]²⁺, where the ligand L is H₂O or NH₃ depending on whether Na₄OH or NH₄OH is used to maintain the <em>p</em>H<em>. </em>Spectrophotometric and potentiometric studies suggest that metal-ligand [ETB] formation constant is highest in the case of Cu(II), and D<em>G</em>⁰ accompanying the Cu-ETB complex formation is also the most negative. The Cu(II), Ni(II) and Co(II) complexes have pseudooctahedral structure as is apparent from their solution magnetic susceptibility and ligand field spectra. <em>Dq </em>(ETB) is exceedingly large for Cu(II), followed by that for Ni(II) and Co(II). The solution data have been corroborated by isolating the BPh₄ salts of the complex cations, viz., [M(H₂O)₄ETB](BPh₄)₂ (M=Cu, Co, Ni), [Ni(NH₃)₄ETB](BPh₄)₂, [Zn(H₂O)₂(ETB)](BPh₄)₂ and [Ni₂(OH)₂(H₂O)₄(ETB)₂](BPh₄)₂.These salts have been characterized by elemental analysis, molar conductance, magnetic susceptibility, EPR (for Cu(II) complex), infrared and UV-visible spectroscopy. The mode of coordination of ETB is also supported by the IH NMR data of Zn(II) complex. This <em>in vitro </em>study is quite consistent with the idea that ETB treatment depletes Cu²⁺ in the physiological system.