Complexation of thyrotropin-releasing hormone and its related compounds with copper(II) and nickel(II) ions

Abstract

The complex formation of L-pyroglutamyl- L-histidyl- L-prolinamide (TRH, HA) with Cu(II) and Ni(II) ions was studied by pH-metry, UV spectroscopy and circular dichroism, for aqueous solutions at an ionic strength I=0.10 mol dm −3 (NaClO 4) and temperature of 25±0.1 °C. N-Acetyl- L-histidine and L-pyroglutamic acid were chosen as reference materials for discussing the results obtained. Analysis of potentiometric data led to the composition and the formation constant of the metal complexes of these ligands. Thus we have found CuA (3.41), CuH −1A (−3.1), CuH −2A (−7.68), CuH −1A 2 (0.9), CuH −2A 2 (−5.75), CuH −3A (−18.3); NiA(2.7), NiH −2A (−14.62) and NiH −3A (−25.2) as TRH complexes (logarithmic overall formation constant). Judging from these results, the predominant species at pH 7–8 should be CuH −2A and NiA, respectively, when intraventricular injection was made with the respective metal complexes into a biological body. The effect of the Ni complex is superior to that of TRH on locomotor activity, which may be interpreted in terms of a weak interaction of Ni(II) ion with TRH, and the apparent indifference of copper(II) ion may be explained in terms of the reduction in potency by stronger bonding with the ligand.